Tumor-associated peptides that bind to mhc-molecules

ABSTRACT

The invention relates to a tumor-associated peptide with an amino acid sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 577 from the attached sequence protocol, the peptide being capable of binding to a molecule of the human major histocompatibility complex (MHC) class I. The invention further relates to the use of the peptides for preparation of a drug and for the treatment of tumor diseases and/or adenomatous diseases. Furthermore, a pharmaceutical composition is described comprising at least one of the peptides.

The present invention relates to tumor-associated peptides that arecapable of binding to a molecule of the human class I majorhistocompatibility complex (MHC). Such peptides are, for example, usedin the immunotherapy of tumor diseases.

The recognition of tumor-associated antigens (TAA) by immune systemcomponents plays a major role in the elimination of tumor cells by theimmune system. This mechanism is based on the prerequisite that thereare qualitative or quantitative differences between tumor cells andnormal cells. In order to achieve an anti-tumor response, the tumorcells have to express antigens that are targets of an immune responsesufficient for elimination of the tumor.

Particularly CD8-expressing cytotoxic T lymphocytes (in the followingtermed CTL) participate in tumor rejection. In order to elicit such animmune reaction by cytotoxic T cells, foreign proteins/peptides must bepresented to the T cells. T cells recognize antigens as peptidefragments only if those are presented on cell surfaces by MHC molecules.These MHC (“major histocompatibility complex”) molecules are peptidereceptors that normally bind peptides within the cell in order totransport them to the cell surface. This peptide/MHC molecule complexcan be recognized by T cells. Human MHC molecules are termed humanleukocyte antigens (HLA).

There are two classes of MHC molecules: MHC class I molecules, presenton most nucleated cells, present peptides that are generated byproteolytic degradation of endogenous proteins. MHC class II moleculesare only found on professional antigen presenting cells (APC), andpresent peptides of exogenous proteins that are engulfed and processedby APC during endocytosis. Complexes formed between peptide and MHCclass I are recognized by CD8-positive cytotoxic T cells, complexesformed between peptide and MHC class II are recognized by CD4 T helpercells.

In order for a peptide to elicit a cellular immune response, it needs tobind to an MHC molecule. This process depends on the allele of the MHCmolecule and on the amino acid sequence of the peptide. Usually, MHCclass I-binding peptides have a length of 8-10 residues, and theirsequences contain two conserved residues (“anchors”) interacting withthe corresponding binding groove of the MHC molecule.

In order for the immune system to be able to elicit an effective CTLresponse against tumor-derived peptides, such peptides not only have tobe able to bind to certain MHC class I molecules being expressed bytumor cells, they also have to be recognized by T cells bearing specificT cell receptors (TCR).

The main purpose for developing a tumor vaccine is the identificationand characterization of tumor-associated antigens being recognized byCD8+ CTL.

The antigens, or their epitopes, that are recognized by thetumor-specific cytotoxic T lymphocytes can be molecules from all proteinclasses, such as enzymes, receptors, transcription factors, etc. Anotherimportant class of tumor-associated antigens are tissue-specificstructures such as CT (“cancer testis”) antigens that are expressed invarious types of tumors and in healthy testicular tissue. For theproteins to be recognized as tumor-specific antigens by cytotoxic Tlymphocytes, and to be therefore used in a therapy, certain conditionsmust be met: The antigen should mainly be expressed by tumor cells andnot or only in smaller amounts by normal cells in contrast to tumors.Furthermore, it is desirable that the respective antigen is present inhigh concentration not only in one type of tumor but in other tumortypes as well. The presence of epitopes in the amino acid sequence ofthe antigen is also absolutely mandatory since such peptides that arederived from a tumor-associated antigen (“immunogenic peptides”), shouldlead to a T cell response, either in vitro or in vivo.

Therefore, TAAs are a starting point for the development of a tumorvaccine. The methods for identifying and characterizing the TAAs arebased on the use of CTL that have already been induced in the patients,or they are based on the generation of differential transcriptionprofiles between tumors and normal tissues.

However, the identification of genes overexpressed in tumor tissues orhuman tumor cell lines, or selectively expressed in such tissues or celllines, does not provide precise information as to the use of theantigens being transcribed from these genes in the immune therapy. Thisis because only individual epitopes of these antigens are suitable forsuch an application since only the antigen epitopes—not the entireantigen—elicit a T cell response through MHC presentation. It istherefore important to select only those peptides from overexpressed orselectively expressed proteins that are presented in connection with MHCmolecules, so targets for the specific recognition of primary cells orof tumor cell lines established from primary tumor tissue cells, bycytotoxic T lymphocytes could be obtained.

Based on this background, it is an objective of the present invention toprovide at least one novel amino acid sequence for such a peptide thatis capable to bind to a molecule of the human major histocompatibilitycomplex (MHC) class I.

According to the invention this objective is addressed by providing atumor-associated peptide with an amino acid sequence selected from thegroup consisting of SEQ ID NO. 1 to SEQ ID NO. 577 in the attachedsequence protocol, whereby the peptide being capable of binding to amolecule of the human major histocompatibility complex (MHC) class I. Inthis way, the objective forming the basis of the invention is addressedcompletely.

It is to be understood that the identified tumor peptides may besynthesized to obtain larger quantities or for the use for the belowdescribed purposes, or may be expressed in cells.

The inventors were able to isolate and identify the above mentionedpeptides from tumor tissue as specific ligands from MHC class Imolecules. The term “tumor-associated” peptides herein refers topeptides that are isolated and identified from tumor material. Thus,these peptides that are presented on true (primary) tumors are subjectedto antigen processing in a tumor cell.

The specific ligands could be used in cancer therapy, e.g. to induce animmune response against tumor cells expressing the respective antigensfrom which the peptides are derived.

Such an immune response in form of an induction of CTL may be obtainedin vivo. In order to obtain such an immune response the peptide isadministered to a patient suffering from a TAA-associated tumor disease,for example in form of a pharmaceutical composition.

On the other hand, a CTL response against a tumor expressing theantigens from which the peptides are derived may also be elicited exvivo. In order to do so, the CTL precursor cells are incubated togetherwith antigen presenting cells and the peptides. Then, the thusstimulated CTL are cultivated, and these activated CTL are administeredto the patient.

Furthermore, it is possible to load APC with the peptides ex vivo, andto administer these loaded APC to the patient expressing in the tumortissue the antigens from which the peptide is derived. Then, the APCthemselves may present the peptide to the CTL in vivo, and therebyactivate them.

However, the peptides according to the invention may also be used asdiagnostic reagents.

Thus, using the peptides it could be found out if CTL are present in aCTL population or have been induced by a therapy that are specificallydirected against a peptide,

The peptides may also be used to test for the increase of precursor Tcells with reactivity against the defined peptide.

Furthermore, the peptide may be used as a marker to track the diseasecourse of a tumor expressing the antigen from which the peptide isderived.

The attached Table 1 lists the identified peptides. The table alsocontains the proteins from which the peptides are derived, and therespective positions of the peptides in the respective proteins whichare named or abbreviated by accepted gene symbols according to the “HUGOGene Nomenclature Committee” (http://www.gene.ucl.ac.uk/nomenclature/ orhttp://www.ncbi.nlm.nih.gov/LocusLink/). The English names of theproteins have been maintained to avoid erroneous translations.Furthermore, the Acc numbers are listed that are used in the gene bankof the “National Center for Bio-technology Information” of the NationalInstitute of Health (see http:\\www.ncbi.nlm.nih.gov).

The inventors were able to isolate the peptides (or ligands) from 8renal cell tumors and 2 glioblastomas from altogether 10 patients,RCC75, RCC98, RCC100, RCC103, RCC112, RCC115, RCCl16, RCC130 and NCH359,as well as NCH361, and from a tumor cell line (J-Y).

From the patients' tumors and the cell line J-Y 577 ligands could beidentified that were bound to the HLA subtypes A*03, B*07, B*40 (RCC75),A*01, A*03, B*07, B*18 (RCC98), A*02, A*03, B*07, B*18 (RCC100), A*11,A*25, B*15, B*44 (RCC103), A*01, A*31, B*08, B*27 (RCC112), A*02, A*03,B*15, B*18 (RCC115), A*O1, A*02, B*27, B*37 (RCC116), A*02, A*24, B*07,B*44 (RCC130), A*03, A*32, B*07, B*35 (NCH359), A*26, B*38 (NCH361) andA*02, B*07 (J-Y).

Some of the ligands are derived from highly expressed so called“housekeeping” genes that are uniformly expressed in most tissues,however, many are characterized by tissue-specific and tumor-specificexpression.

Thus, several peptides could be identified that are derived fromproteins which are especially overexpressed in tumor tissue. Forexample, fragments of tenascin-C (GLAPSIRTK, SEQ ID NO. 2) could beidentified (Herold-Mende et al., Clinical impact and Functional Aspectsof Tenascin-C Expression during Glioma Progression, 2002, Int. J.Cancer, 98: 362-369).

Also, the inventors were able to identify ligands, among others, thatare derived from SOX9 (YPHLHNAEL, SEQ ID NO. 7) and RGS5 (LAALPHSCL, SEQID NO. 448).

As primary tumor cells are not suited for in vitro culture, theinventors have chosen a human tumor cell line as an example in order toadditionally demonstrate that peptides according to the inventionidentified from this cell line, are suited to activate cytotoxic Tlymphocytes in vitro. Particularly, the inventors could show that usinga peptide from the established tumor cell line JY as an example, it waspossible to generate cytotoxic T lymphocytes (CTL) in vitro that arespecific for the selected peptide with the sequence FPSLREAAL (MAGEA1,position 294-302) and SEQ ID NO. 114 and the HLA allele B*0702. Usingthese CTL, KM22 target cells loaded with the SEQ ID NO. 114 peptidecould be selectively killed, whereas KM22 control target cells notloaded with the SEQ ID NO. 114 peptide were not recognized by thecytotoxic T cells. Thus, it could be shown exemplified that human Tcells could be activated in vitro using the peptides according to theinvention as epitopes. Furthermore, it could be demonstrated that thecytotoxic T lymphocytes lysing the T2 cells loaded with the SEQ ID NO.114 peptide also express interferon gamma which has been described as areliable marker for the activation of T cells.

In a preferred embodiment, it is also possible to use peptides forstimulating an immune response that comprise sequence ID NO. 1 to 577,and in which at least one amino acid has been replaced by another aminoacid with similar chemical properties.

Referring to the corresponding MHC subtypes, these are, for example, theanchor amino acids that may be replaced by amino acids with similarchemical properties. Thus, for example, in peptides associated with theMHC subtype HLA-A*2, leucine on position 2 may be replaced byisoleucine, valine or methionine and vice versa, and at the C-terminusleucine by valine, isoleucine and alanine, each containing non-polarside chains.

Furthermore it is possible to use peptides with sequence ID No. 1 to 577comprising at least one additional amino acid N- or/and C-terminally, orin which at least one amino acid is deleted.

Furthermore, peptides with sequence ID No. 1 to 577 may be used in whichat least one amino acid is chemically modified.

The varying amino acid(s) is (are) selected in such way that thevariation does not affect the immunogenicity of the peptide, i.e.demonstrates a similar binding affinity to the MHC molecule and thecapability for T cell stimulation.

According to the invention, the peptide may be used for treatment oftumor diseases and/or adenomatous diseases.

The tumor diseases to be treated comprise, for example, kidney, brain,mammary, pancreas, gastric, testicular and/or skin cancers and tumordiseases of the nerve system. This list of tumor diseases is onlyexemplary, and is not intended to limit the area of application. Theinventors were able to show in independent studies that the peptidesaccording to the invention are suitable for such use. In these studiesit was shown that specifically generated CTL that are specific forcertain peptides were able to kill tumor cells effectively andselectively.

Basically, for the use of tumor-associated antigens in a tumor vaccine,several application forms are possible. For example, Tighe et al. 1998,Gene vaccination: plasmid DNA is more than just a blueprint, Immunol.Today 19(2):89-97, described that the antigen may be administered eitheras recombinant protein together with suitable adjuvants or carriersystems, or in form of the cDNA encoding the antigen in plasmid vectors.For this, the antigen needs to be processed and presented by antigenpresenting cells (APC) in the patient's body in order for an immuneresponse to be induced.

Melief et al., 1996, Peptide-based cancer vaccines, Curr. Opin. Immunol.8:651-657, demonstrated another option, namely the use of syntheticpeptides as a vaccine.

For this purpose, the peptide may be used in a preferred embodimenttogether with added adjuvants, or alone.

As an adjuvant, for example, the granulocyte macrophage colonystimulating factor (GMCSF) may be used. Further examples for suchadjuvants are aluminum hydroxide, mineral oil emulsions such as, forexample, Freund's adjuvant, saponins or silicon compounds.

The use of adjuvants provides the advantage that the immune responseinduced by the peptide may be enhanced, and/or the peptide may bestabilized.

In another preferred embodiment, the peptide is used bound onto anantigen presenting cell. This measure provides the advantage that thepeptides can be presented to the immune system, particularly cytotoxic Tlymphocytes (CTL). By this, the CTL are able to recognize the tumorcells and specifically kill them. Suitable as antigen presenting cellsfor such an application are, for example, dendritic cells, monocytes orB lymphocytes.

For this purpose, the cells are, for example, loaded with peptides exvivo. On the other hand, it is also possible to transfect the cells withDNA encoding the peptides or with the corresponding RNA to express thepeptide on the cells.

The inventors were able to show in independent studies that it ispossible to load dendritic cells (DC) with specific peptides, and thatthese loaded dendritic cells activate peptide-specific CTL. This meansthat the immune system can be stimulated to raise CTL against the tumorsexpressing the respective peptides.

The antigen presenting cells carrying the peptide may be used eitherdirectly or may be activated prior to their use, for example with theheat shock protein gp96. This heat shock protein induces the expressionof MHC class 1 molecules and co-stimulatory molecules such as B7, andalso stimulates the production of cytokines. Together, this supports theinduction of immune responses.

In another preferred embodiment, the peptides are used to labelleukocytes, especially T lymphocytes.

This application is advantageous if it is intended to use the peptidesto find out if CTL are present in a CTL population that are specificallydirected against a peptide.

Furthermore, the peptide may be used as a marker to evaluate theprogress of a therapy for a tumor disease.

The peptide may be used in other immunizations or therapies formonitoring the therapy as well. Therefore, the peptide may not only beused therapeutically but also diagnostically.

In another embodiment, the peptides are used to generate an antibody.

Polyclonal antibodies may be obtained conventionally by immunizinganimals by injection of the peptides and subsequent purification of theimmunoglobulin.

Monoclonal antibodies may be generated according to standard protocols,such as, for example, described in Methods Enzymol. (1986), 121,Hybridoma technology and monoclonal antibodies.

In another aspect the invention also relates to a pharmaceuticalcomposition comprising one or more of the peptides.

This composition is used, for example, for parenteral administration,such as subcutaneous, intradermal or intramuscular, or for oralapplication. For this, the peptides are solved or suspended in apharmaceutically acceptable, preferably aqueous carrier. Furthermore,the composition may contain excipients such as buffers, binders,diluents, etc.

The peptides may also be given together with immunostimulatorysubstances such as cytokines. A comprehensive description of excipientsthat may be used in such compositions is given, for example in A. Kibbe,Handbook of Pharmaceutical Excipients, 3. Ed., 2000, AmericanPharmaceutical Association and pharmaceutical press.

The preparation may be used for prevention, prophylaxis and/or therapyof tumor diseases and/or adenomatous diseases.

The pharmaceutical preparation containing at least one of the peptideswith sequence ID NO. 1 to 577 will be administered to a patientsuffering from a tumor disease with which the respective peptide orantigen is associated. Thus, a tumor-specific immune response based ontumor-specific CTL can be elicited.

The amount of the peptide or peptides in the pharmaceutical compositionis present in a therapeutically effective amount.

The peptides that are present in the composition may also bind to atleast two different HLA types.

In a further aspect, the present invention relates to nucleic acidmolecules encoding the peptides with sequence ID NO. 1 to 577.

The nucleic acid molecules may be DNA or RNA molecules, and may also beused for immune therapy of cancer diseases. The peptide which isexpressed from the nucleic acid molecule induces an immune responseagainst tumor cells expressing the peptide.

According to the invention, the nucleic acid molecules may also bepresent in a vector.

Furthermore, the invention relates to cells which have been geneticallyaltered using a nucleic acid molecule encoding the peptides so that theyproduce a peptide with the sequence ID NO. 1 to 577.

For this purpose, the cells are transfected with the DNA encoding thepeptides, or with the respective RNA, whereby the peptides are made tobe expressed on the cells. As antigen presenting cells for such anapproach are suited, for example, dendritic cells, monocytes or Blymphocytes.

It is to be understood that the features that have been mentioned aboveand that are yet to be discussed below, are suitable not only in therespectively described combination but also alone, without leaving thescope of the present invention.

Embodiments of the invention are presented and discussed in thefollowing examples and in the attached figures.

FIG. 1 a shows the negative control regarding CTL-specific lysis of KM22target cells (without peptide);

FIG. 1 b shows the CTL-specific lysis of KM22 target cells pulsed withpeptide and treated with interferon gamma.

FIG. 2 shows the production of interferon gamma by specific Tlymphocytes upon stimulation by KM22 or JY cells loaded with peptide.

FIG. 3 shows the peptide-specific stimulation of human CD8-positive Tcells, and

FIG. 4 shows the detection of peptide-specific T cells in blood fromrenal cell carcinoma patients.

FIG. 5 shows the tetramer analysis of microsphere-driven proliferationof B*0702/IARNLTQQL-specific CD8+ lymphocytes from peripheral blood.Four (4) out of 6 tested donors (HD155, 159, 161, 177) had significant Tcell responses (above the red line) that were directed specificallyagainst the tested peptide antigen with SEQ ID NO. 233, as could beshown by detection of peptide/HLA-B*0702 complex-specific T cellreceptors by tetramer staining.

EXAMPLE 1 1.1 Patient Samples

Eight samples were obtained from the Department of Urology at theUniversity of Tübingen, Tübingen, Germany, that were derived frompatients with histologically confirmed renal cell carcinoma. The patienttermed RCC75 had the following HLA haplotype: A*03, B*07, B*40. Thepatient termed RCC98 had the following HLA haplotype: A*01, A*03, B*07,B*18, The patient termed RCC100 had the following HLA haplotype: A*02,A*03 B*07, B*18. The patient termed RCC103 had the following HLAhaplotype: A*11, A*25, B*15, B*44. The patient termed RCC112 had thefollowing HLA haplotype: A*01, A*31, B*08, B*27. The patient termedRCC115 had following the HLA haplotype: A*02, A*03, B*15, B*18, Thepatient termed RCC116 had the following HLA haplotype: A*01, A*02, B*27,B*37, and the patient termed RCC130 had following HLA haplotype: A*02,A*24, B*07, B*44.

Two samples were obtained from the Department of Neurosurgery,University of Heidelberg, Heidelberg, Germany, that were derived frompatients with histologically confirmed glioblastomas. The patient termedNCH359 had the following HLA haplotype: A*03, A*32, B*07, B*35. Thepatient termed NCH361 had following HLA haplotype: A*26 and B*38.

1.2. Isolation of MHC Class I-Bound Peptides

Shock frozen tumor samples were processed as previously described inSchirle, M. et al., Identification of tumor-associated MHC class Iligands by a novel T cell-independent approach, 2000, European Journalof Immunology, 30:2216-2225. The peptides were isolated according tostandard protocols, using the monoclonal antibody W6/32 which isspecific for HLA class 1 molecules, or using the monoclonal antibodyBB7.2 which is specific for HLA-A2. Barnstable, C. J. et al., Productionof monoclonal antibodies to group A erythrocytes, HLA and other humancell surface antigens-new tools for genetic analysis, 1978, Cell,14:9-20, and Parham, P. & Brodsky, F. M., Partial purification and someproperties of BB7.2. A cytotoxic monoclonal antibody with specificityfor HLA-A2 and a variant of HLA-A28, 1981, Hum. Immunol., 3:277-299,have described generation and use of these antibodies.

1.3. Mass Spectroscopy

The peptides were separated by “reversed phase HPLC” (SMART system, μRPCC2/C18 SC 2.1/19, Amersham Pharmacia Biotech), and the obtainedfractions were analyzed by nanoESI MS. The approach corresponded to theapproach described by Schirle, M. et al., Identification oftumor-associated MHC class I ligands by a novel T cell-independentapproach, 2000, European Journal of Immunology, 30:2216-2225.

The peptides obtained from tumor tissue were identified by capillary LCMS, as just described, however with minor modifications: 100 μL of eachsample were loaded, desalted and pre-concentrated on a 300 μm*5 mm C18μguard column (LC Packings). Solvent and sample were added using asyringe pump (PHD 2000, Harvard Apparatur, Inc.) with a sealed 100 μLsyringe (1710 RNR, Hamilton) at a speed of 2 μL/min. For separation ofthe peptides, the pre-concentration column was installed before a 75μm*250 mm C18 column (LC Packings). Then, a binary gradient with 25-60%B was run for 70 min. during which time the flow rate was reduced from12 μL/min to approximately 300 nL/min. using a TEE connector (ZTIC,Valco) and a 300 μm*150 mm C18 column.

To ensure that the system was free from peptide residues, a blank wasmeasured respectively. Online-fragmentation was performed as described,and the spectra of the fragments were analyzed manually. Data basesearches (NCBInr, EST) were performed using MASCOT(http://www.matrixscience.com).

1.4. Identification of the MHC Class I Ligands

In the attached sequence protocol and in the attached table 1 theligands are listed that were bound to the HLA molecules of patientsRCC75, RCC98, RCC100, RCC103, RCC112, RCC115, RCC116, RCC130, NCH359 andNCH361. The peptides associated with HLA-A*02 had an allele-specificpeptide motif: on position 2, leucine, valine, isoleucine, alanine, ormethionine were found, and at the C-terminus leucine, valine,isoleucine, or alanine. Most of the ligands were derived from so-called“housekeeping” proteins, however, ligands from tumor-associated proteinscould be identified as well. For example, fragments from tenascin-Ccould be identified (GLAPSIRTK, SEQ ID NO. 2; GVLKKVIRH, SEQ ID NO. 20).Herold-Mende et al., Clinical Impact and Functional Aspects ofTenascin-C Expression during Glioma Progression, 2002, Int. J. Cancer,9S: 362-369, show that in general the strength of the expression of theextracellular matrix protein tenascin-C correlates with the severity ofthe disease and the immigration of tumor cells in healthy tissue.

1.5. Detection of Peptide-Specific T Cells in the Normal CD8+ T CellRepertoire

For detection of peptide-specific T cells, for example specific for thepeptide with the sequence FPSLREAAL (SEQ ID NO. 114), mononuclear cellsfrom peripheral blood of healthy subjects were stained with thecorresponding HLA-A* subtype tetramers constituted with the respectivepeptides: To generate the tetramers, recombinant HLA-B* subtypemolecules were constituted in vitro with the peptides, purified by gelfiltration, biotinylated, and mixed with streptavidin for linking themonomers, as described by Walter S. et al., 2003, Cutting EdgePredetermined Avidity of Human CDS T Cells Expanded on CalibratedMHC/Anti-CD2S-Coated Microspheres, J. Immunol. 171: 4974-4978.

Basically, the results of the double staining are measured by FACSanalysis, and the specific binding of the peptide tetramers is detected(Walter S. et al., 2003, Cutting Edge: Predetermined Avidity of HumanCDS T Cells Expanded on Calibrated MHC/Anti-CD2S-Coated Microspheres, J.Immunol. 171: 4974-4978).

EXAMPLE 2

To analyze the presentation of the selected peptides by tumor cells andthe recognition of the peptides by CTL, CTL were induced in vitro thatare specific for the chosen peptides. For this purpose, KM22 and JYtarget cell lines were used.

2.1. Recovery of the Specific T Lymphocytes

Specific T lymphocytes were isolated from the blood of healthy subjectsas described in 1.5 and concentrated by FACS sorting.

2.2. Peptide Synthesis

The peptides chosen as an example were synthesized using F-moc(9-fluorenylmethyloxycarbonyl) protection groups on a peptidesynthesizer (432A, Applied Biosystems, Weiterstadt, Germany) andanalyzed by “reversed phase” HPLC and mass spectroscopy. Thereby,sufficient amounts of the identified peptides could be produced.

2.3. Induction of an Antigen-Specific CTl Response Using RestrictedSynthetic Peptides

For CTL induction, the T lymphocytes obtained in step 2.1 (5×10⁶ Tlymphocytes per well) were co-incubated by in vitro restimulation in24-well plates with 1×10⁶ irradiated target cells per well in 1.5 mL Tcell medium [consisting of RPMI 1640, 25 mM HEPES (LifeTechnologies/Invitrogen, Karlsruhe, Germany)] with 10% heat-inactivatedhuman AB serum (CC Pro, Neustadt/Weinstraβe, Germany), 2 mM L-glutamine,50 U/mL penicillin, 50 mg/mL streptomycin, and 20 μg/mL gentamicine (allfrom Bio Whittaker/Cambrex, Verviers, Belgium). Additionally, 5 ng/mLhuman IL-12 p70 (R&D Systems) were added. After approximately 4 daysco-incubation at 37° C., fresh medium was added with 20 U/mL human IL-2(R&D Systems), and the cells were incubated for another 3 to 4 days.This stimulation cycle was repeated twice.

2.4. CTL Assay

For the CTL assays, KM22 and JY tumor cell lines were used as targetcells. Peptide-pulsed cells were pulsed with 50 μg/mL peptide for 2hours. All target cells were labeled in RP10 medium (RPMI 1640,supplemented with 10% heat-inactivated fetal calf serum and antibiotics)for 1 hour at 37° C. with [⁵¹Cr] sodium chromate (⁵¹Cr). Then, 10⁴cells/well were added to a 96-well round bottom plate. Various numbersof CTL were added to obtain an end volume of 200 μL, with subsequentincubation for 4 hrs at 37° C. Then, supernatants (500 μL/well) wereharvested and counted in a beta-plate counter. Specific lysis wascalculated in percent as follows: 100×(experimental release−spontaneousrelease/maximum release−spontaneous release). Each, spontaneous andmaximum release were determined in presence of either medium or 2%Triton X-100.

2.5. Results of the CTL Induction

a) CTL Cytotoxic Activity Compared to Peptide-Pulsed Target Cells

In ⁵¹Cr release assays (see 2.4.) the cytotoxic activity of induced CTL(see 2.3.) was tested and compared to KM22 and JY cells. Cell lines KM22and JY are HLA-B*07 positive.

The results of these release assays are shown in FIGS. 1 a and 1 b. InFIGS. 1 a and 1 b, the abbreviation “IFN” stands for interferon gamma,“E:T” stands for the ratio of effector to target cells, “Tet+” standsfor T lymphocytes binding to HLA-B*0702/FPSLREAAL tetramers, and “Tet−”stands for T lymphocytes not binding to HLA-B*0702/FPSLREAAL tetramers.

The results show that an antigen-specific kill of the cells can beobtained with CTL cell lines that have been obtained after restimulationfor 2 weeks.

In FIG. 1 a is shown that KM22 target cells treated with interferongamma and positive for HLA allele B*0702 without peptide were notrecognized by specific cytotoxic T lymphocytes. FIG. 1 b shows that KM22target cells, treated with interferon gamma, positive for HLA alleleB*0702 presenting the peptide with the sequence FPSLREAAL from the tumorantigen MAGE-1 are recognized and lysed by specific cytotoxic Tlymphocytes. Thus, only those cells were killed by an increasing numberof CTL that presented the respective selected peptides; the controlcells loaded with irrelevant peptides were not killed. By this, thespecificity of the cytolytic activity could be demonstrated.

b) Production of Interferon Gamma by Peptide-Stimulated T Lymphocytes

In another experiment it was shown that the cytotoxic T lymphocyteslysing the T2 cells loaded with peptide FPSLREAAL (SEQ-ID NO. 114) alsoexpressed interferon gamma which has been described as a reliable markerfor activation of T cells.

In FIG. 2, the results of the measurements are shown, with KM22 and JYcells being tested. The same abbreviations as in FIG. 1 were used, with“CD8+” describing T lymphocytes expressing the receptor molecule CD8 onthe cell surface.

To detect IFN gamma, 1×10⁵ effector cells and stimulator cells that havebeen pulsed with peptide were grown in T cell medium on 96-well plates(T cell medium: RPMI 1640 with 25 mM HEPES (Gibco/Invitrogen, Karlsruhe,Germany; supplemented with 10% heat-inactivated human AB serum (CC pro,Neustadt/W., Germany; 2 mM L-glutamine, 50 U/mL penicillin, 50 μg/mLstreptomycin and 20 μg/mL gentamycine (all from BioWhittaker). Theloading with peptides was conducted in X-Vivo 15 medium with therespective peptides für approx. 2 hrs at 37° C.

After 1 to 2 hrs GolgiStop (Becton Dickinson) was added and incubatedfor another 4 to 5 hrs. Then, the cells were permeabilized and stainedby using the Cytofix/Cytoperm Plus kit as well as anti-CD4-FITC,anti-IFN-γ-PE and anti-CD8-PerCP according to the manufacturer'srecommendations (Becton Dickinson). The cytometric analysis wasperformed using a FACSCalibur cytometer.

As can be seen from FIG. 2, T lymphocytes binding toHLA-B*0702/FPSLREAAL tetramer (=specific T lymphocytes, “Tet+”) produceinterferon gamma, when they are stimulated with KM22 or JY cells, eachpretreated with various amounts of interferon gamma and loaded withpeptide with SEQ ID NO. 114 (see FIG. 2, “KM22+FPSLREAAL” and“JY+FPSLREAAL”, each pretreated with 5 or 25 μM INF). In contrast,unspecific T lymphocytes (which do not bind to the HLA-B*0702/FPSLREAALtetramer) do not produce any interferon gamma (=“Tet−”).

Furthermore, FIG. 2 shows that neither the specific (=“Tet+”) nor theunspecific (“Tet−”) T lymphocytes produced interferon gamma if they werestimulated with an unspecific control peptide (in FIG. 2 as an example:APRTVALTA, SEQ ID NO. 585) (see FIG. 2 for “Tet+” and “Tet−”,respectively: “KM22+APRTVALTA” and “JY+APRTVALTA”, each pretreated with25 μM INF).

c) Peptide-Specific Stimulation of CD8-Positive T Cells

For further determination of the peptide-specific stimulation ofCD8-positive T cells the peptide with sequence LAALPHSCL (SEQ ID NO.448) from protein RGS-5 and the control peptide with sequence ELAGIGILTV(SEQ ID NO. 578) from melanoma antigen MELAN-A (position 26-35, modifiedby an amino acid exchange of the alanine at position 27 by leucine) weresynthesized using standard Fmoc chemistry, with the control peptide alsobinding to the HLA allele A*02. Biotinylated recombinant A*02 moleculesand fluorescent MHC tetramers were generated as described by Altman etal. (“Phenotypic analysis of antigen-specific T lymphocytes”, Science274:94, 1996). To generate artificial antigen presenting cells (“APCs”),streptavidin-coated polystyrene particles (5.6 μm diameter) with abinding capacity of 0.064 μg biotin-FITC/mg microspheres (BangsLaboratories, Fishers, Ill., USA) were resuspended with 2×10⁶particles/mL in a buffer containing the biotinylated MHC and theantibodies, and incubated for 30 min. at room temperature.

For the antigen-specific in vitro stimulation of the human CD8 T cells,PBMC from fresh buffy coat were isolated by standard gradientseparation. Untreated CD8 T cells were concentrated by negativedepletion using MACS (Miltenyi Biotec, Bergisch Gladbach, Germany). Thein vitro stimulations were performed on 24-well plates with 5×10⁶responder cells and 1×10⁶ beads or 1×10⁶ irradiated APCs per well in 1.5mL T cell medium (compare supra). 5 ng/mL human IL-12 p70 (R&D Systems,USA) were added together with microspheres. After 3 to 4 daysco-incubation at 37° C., fresh medium and 20 U/mL human IL-2 (R&DSystems, USA) were added, and the cells were incubated for another 3 to4 days. This stimulation cycle was repeated twice.

For the cell surface and intracellular cytometric analysis, tetrameranalyses with fluorescent MHC tetramers plus anti-CD8 antibodies(hybridoma UKT8) were conducted on a four-color FACSCalibur (BectonDickinson).

The results of these analyses are shown in FIG. 3. It can be seen thatthe RGS-5 peptide with SEQ ID NO. 448 specifically stimulates humanCD8-positive T cells. In FIG. 3, in the left column, the analysis ofPBMC T cells is shown that have been stimulated twice with a controlpeptide with the sequence ELAGIGILTV from melan-A (SEQ ID NO. 578), asdescribed above.

The right column shows the analyses of T cells that have been stimulatedwith the RGS-5 peptide with the sequence LAALPHSCL (SEQ ID NO. 448).

In the top left of FIG. 3 is shown that CD8-positive α-axis) T cellsstimulated with melan-A peptide/MHC-A*02 tetramer complexes do not bindto MHC-A*02 tetramers complexed with the peptide with the sequenceLAALPHSCL (SEQ ID NO. 448) (y-axis).

In the top right of FIG. 3 is shown that CD8-positive T cells,stimulated with RGS-5 peptide with the sequence LAALPHSCL/MHC-A*02tetramer complexes, bind to MHC-A*02 tetramers complexed with thepeptide with the sequence LAALPHSCL (SEQ ID NO. 448) (y-axis). Thedouble-stained (double-positive) cells are shown in the upper rightquadrant.

In FIG. 3, left middle, is shown that CD8-positive T cells (x-axis)stimulated with melan-1 peptide/MHC-A*02 tetramer complexes, bind toMHC-A*02 tetramers complexed with the peptide with the sequenceELAGIGILTV (SEQ ID NO. 579) from melan-A (y-axis). The double stained(double positive) cells are shown in the upper right quadrant. In theright middle is shown that CD8-positive T cells, stimulated withcomplexes from RGS-5 peptide with the sequence LAALPHSCL and MHC-A*02tetramers, not bind to MHC-A*02 tetramers complexed with the peptidewith the sequence ELAGIGILTV (SEQ ID NO. 579) from melan-A (y-axis).

In the bottom row of FIG. 3, on the left hand side, the proportionalnumbers of the melan-A/MHC-A*02-specific T cells are shown by doublestaining with the two applied MHC tetramer-peptide complexes(melan-A/MHC-A*02 and RGS-5/MHC-A*02). After prior stimulation withmelan-A peptide/MHC-A*02 tetramer complexes bound on artificial antigenpresenting cells, 19.3% of the stimulated cells bind specifically to theMHC tetramer complex of melan-A peptide and HLA-A*02. On the bottomright hand side, the proportional numbers of the RGS-5/MHC-A*02-specificT cells are shown by double staining with the two applied MHC tetramercomplexes (melan-A/MHC-A*02 and RGS-5/MHC-A*02). After prior stimulationwith RGS-5 peptide/MHC-A*02 tetramer complexes bound on artificialantigen presenting cells, 8.0% of the stimulated cells bind specificallyto the MHC tetramer complex of RGS-5 peptide with the sequence LAALPHSCL(SEQ ID NO. 448) and HLA-A*02.

d) Detection of Peptide-Specific T Cells in Blood from Renal CellCarcinoma Patients

In further experiments, peptide-specific T cells from blood from renalcell carcinoma patients previously immunized with peptide-loadedautologous dendritic cells could be detected.

For this detection, a quantitative real-time polymerase chain reaction(RT-PCR) was performed. This RT-PCR was conducted as described byKammula et al. (Kammula et al., Journal of Immunology 163:6867, 2000).For this, PBMCs were thawed in T cell medium, plated out with 1×10⁶cells in 500 μL medium and incubated over night with 5% CO₂ at 37° C.Then, the synthetic peptides were added with 5 μg/mL for 3 hours, andthen an RNA extraction with Trizole (Invitrogen, Karlsruhe, Germany) wasperformed. The cDNA was transcribed using random hexamer primers(Amersham Biosciences, Freiburg, Germany) and M-MLV reversetranscriptase (Promega GmbH, Mannheim, Germany).

The quantitative RT-PCR was performed on an “ABIPrism 7000 SequenceDetection System” (Applied Biosystems, Darmstadt, Germany) in duplicatein respect to IFN gamma mRNA and CD8 mRNA, using the Taqman PCR mastermix (Applied Biosystems), specific primers and fluorescent probes.

The results represent the copy number of IFN gamma mRNA, with eachsample being normalized regarding the CD8 mRNA copy number (used asreference gene product) (stimulation index).

The gene expression in presence of the tested peptides is relative tothe gene expression obtained in presence of the controls (HLA-A*02epitope derived from HIV1 pol with the sequence ILKEPVHGV, SEQ ID NO.579) (copy number of the control was set to 1).

In FIG. 4 the results of these studies are shown. The diagram in FIG. 4shows the ex vivo T cell activation after immunization of the patientRCC98 at the University Hospital in Tübingen with nine HLA-bindingpeptides. The first two out of 11 column blocks show the negative andpositive controls of the T cell experiment. The error bars represent thestandard deviation. As mentioned above, the HIV peptide with thesequence ILKEPVHGV (from the viral antigen HIV1 pol, position 896-904;SEQ ID NO. 579) was used as negative control. The negative control didnot lead to a T cell response if the patient was seronegative for HIV.As a positive control, a mixture of peptides from influenza matrix 58-66(GILGFVFTL; SEQ ID NO. 580), HCMVA pp 65 495-503 (NLVPMVATV; SEQ ID NO.581), EBNA6-EBV 284293 (LLDFVRFMGV; SEQ ID NO. 582), IE63-EBV 259-267(GLCTLV AML; SEQ ID NO. 583), and LMP2-EBV 294-302 (CLGGLLTMV; SEQ IDNO. 584) was used, with which as very strong T cell response could beexpected (“posmix”; Maximum: stimulation index 43.6). All controlpeptides for PBMC stimulation were used in a concentration of 5 μg/mL.The background was defined as standard deviation of the negative control(stimulation index 1.35, shown as horizontal dashed line).

In FIG. 4, the next nine column blocks of the diagram show the T cellactivations measured against nine immunized peptides. These ninepeptides were administered together subcutaneously, altogether seventimes in increments of 14 days, loaded onto autologous dendritic cells.Therefore, each column block consists of eight columns (before the1^(st) immunization, after the 1^(st) immunization, after the 2^(nd)immunization, etc.). Therefore, each column block shows the progressionof the T cell responses in the course of the immunizations.

Starting after the 3^(rd) immunization already, strong T cell responseswere obtained for GLASFKSFLK (RGS-5 74-83, SEQ ID NO. 153) andSLLTSSKGQLQK (ADFP 369-380, SEQ ID NO. 289), whereby for the lastpeptide the T cell responses increased after the 4^(th) immunization.Such fluctuations of the T cell response during the course of animmunization therapy are known from other patients as well.

For IARNLTQQL (ADFP 313-321; SEQ ID NO. 233), GPALGRSFL (TNFSF7 78-86,SEQ ID NO. 577) the T cell responses were clearly in the background, andwere weaker for a known pan-HLA DR-binding (PADRE) peptide. For thesethree peptides, an increase of the T cell response was also observedduring the course of the immunization therapy (dotted lines). Thisconfirmed that these three latter peptides have elicited a positive Tcell response.

The patient was immunized as part of a registered clinical study at theUniversity Hospital in Tübingen, Germany. The clinical study was appliedand approved in written form by the Ethical Committee of the Universityof Tübingen, Germany. The study was conducted according to the rules andregulations of the German Medicines Act (Arzneimittelgesetz) and thegood clinical practice (GCP).

In summary, the inventors were thereby able to show that the identifiedpeptides represent promising substances as part of an immunotherapy fora variety of (tumor) diseases.

EXAMPLE 3

Tetramer analysis of the microsphere-driven proliferation ofB*0702/IARNLTQQL (SEQ ID NO. 233)-specific CD8+ lymphocytes fromperipheral blood (see FIG. 5).

1×10⁶ CD8+ enriched PBMCs per well from six healthy HLA-A*0201⁺ donorsHD155, HD159, HD161, HD167, 00168 and 00177, were stimulated weekly withmicrospheres coupled to anti-CD28 plus irrelevant antigen (“irrelevantstimulation”), tumor antigen B*0702/IARNLTQQL with high density (“HD”)or tumor antigen B*0702/IARNLTQQL with low density (“LD”) as previouslyshown [Walter, S, et al. Cutting Edge:

Predetermined avidity of human CD8 T cells expanded on calibratedMHC/anti-CD28-coated microspheres. J. Immunol. 171 (1 0):4974-8, 2003]with minor modifications. After three stimulations in vitro, individualwells were stained with antibody CD8 plus tetramer B*0702/IARNLTQQL.Each dot represents the percentage of tetramer+among CD8+ lymphocytesfrom one well.

Based on the distribution of observed responses after irrelevantstimulation in individual donors, a significant threshold wascalculated, and shown by a horizontal red line using the followingformula:

Threshold=upper limit of 95% confidence interval for the mean+3×upperlimit of 95% confidence interval for the standard deviation

The numbers in the diagrams show the number of significantly positivewells among total wells for the indicated condition.

TABLE 1 Position/ Sequence Gene symbol Acc. No. SEQ ID NO. Sequences ofNCH359 1. VPDSSGPERIL 78-88 NP_002131.2 SEQ ID NO. 1 HNRPK 2. GLAPSIRTK1510-1518 NP_002151.1 SEQ ID NO. 2 TNC 3. RLFEHPLYR 149-157 NP_064608.1SEQ ID NO. 3 FAM20C 4. TPSEPHPVL 381-389 NP_057342.1 SEQ ID NO. 4 HGRG85. QIFVKTLTGK 2-11 AAH01392.1 SEQ ID NO. 5 RPS27A 6. SLMHSFILK 44-52NP_054902.1 SEQ ID NO. 6 DNCL2A 7. YPHLHNAEL 127-135 NP_000337.1 SEQ IDNO. 7 SOX9 8. RLFVGSIPK 244-252 NP_006363 SEQ ID NO. 8 SYNCRIP 9.RVFPDKGYSF 233-242 NP_071320.1 SEQ ID NO. 9 TIA1 10. SLYKKLEIK 554-562NP_003039.2 SEQ ID NO. 10 SLC9A2 11. HPVSDHEATL 216-225 NP_002108 SEQ IDNO. 11 HLA-C 12. LPTRVDFSL 46-54 BAC87610 SEQ ID NO. 12 Symbol does notexist; Gene type: unnamed protein product 13. KSFGSAQEFAW 386-396NP_004757 SEQ ID NO. 13 COPB2 14. SPSTSRTPLL 1026-1035 NP_005219.2 SEQID NO. 14 EGFR 15. STFDSPAHW 1149-1157 NP_005219.2 SEQ ID NO. 15 EGFR16. APEEHPVLL 97-105 NP_001092.1 SEQ ID NO. 16 ACTB 17. RQITQVYGF117-125 NP_002712.1 SEQ ID NO. 17 PPP6C 18. KVSDYILQH 1046-1054NP_054729.3 SEQ ID NO. 18 ASTN2 19. KLLPSVVLK 2-10 NP_001936.1 SEQ IDNO. 19 DTR 20. GVLKKVIRH 23-31 NP_002151.1 SEQ ID NO. 20 TNC 21.KLFDHAVSKF 40-49 NP_004449.1 SEQ ID NO. 21 ACSL4 22. ITVLTKPLPV 112-121NP_002839.1 SEQ ID NO. 22 PTPRO 23. HPVHPDIKL 130-138 NP_057250.1 SEQ IDNO. 23 PIAS1 24. IPRAALLPLL 3-12 NP_002766.1 SEQ ID NO. 24 PRSS11 25.ATNRITVTW 254-262 NP_056981.2 SEQ ID NO. 25 PIASY 26. KIADRFLLY 29-37NP_006760.1 SEQ ID NO. 26 LMO4 Sequences of NCH361 27. DHDPVDKIVL150-159 NP_002128.1 SEQ ID NO. 27 HNRPA2B1 28. DHHQEVIGF 165-173NP_055427.2 SEQ ID NO. 28 C9ORF10 29. IHDLDNISF 188-196 NP_002785.1 SEQID NO. 29 PSMB2 30. DHINDIIKI 834-842 NP_003861.1 SEQ ID NO. 30 IQGAP131. DHMRFISEL 355-363 NP_055423.1 SEQ ID NO. 31 CYFIP1 32. THSLPVVVI456-464 NP_003141.2 SEQ ID NO. 32 STAT3 33. MPVGPDAILRY 929-939NP_004630.2 SEQ ID NO. 33 BAT3 34. RLDDAIHVL 406-414 NP_003196.1 SEQ IDNO. 34 TCF12 35. QHEGTVNIF 1953-1961 NP_002842.1 SEQ ID NO. 35 PTPRZ136. ETVNIWTHF 48-56 NP_940798 SEQ ID NO. 36 PAQR6 37. VHILDTETF 195-203NP_055130.1 SEQ ID NO. 37 KLHDC2 38. QTPDFTPTKY 607-616 NP_055850.1 SEQID NO. 38 ZHX3 39. RHVEVFELL 133-141 NP_003820.1 SEQ ID NO. 39 MPDZ 40.TTIDIGVKY 136-144 NP_001830.1 SEQ ID NO. 40 CNN3 41. DLIEHFSQF 113-121NP_006796.1 SEQ ID NO. 41 HNRPA0 42. ETVWRLEEF 65-73 NP_061984 SEQ IDNO. 42 HLA-DRA 43. DVLESVNLL 176-184 NP_004059.2 SEQ ID NO. 43 AP2M1 44.IHDDFVTTF 466-474 NP_001120.2 SEQ ID NO. 44 AEBP1 45. IHIPINNII 57-65NP_055117.1 SEQ ID NO. 45 Sec61G 46. IHLIDPNTL 281-289 NP_057022.2 SEQID NO. 46 CGI-07 47. IHVIGGNDV 1016-1024 XP_291055.1 SEQ ID NO. 47KIAA1268 48. KAFQKIVVL 291-299 NP_055485.2 SEQ ID NO. 48 BZW1 49.YQDLLNVKL 349-357 NP_002046.1 SEQ ID NO. 49 GFAP 50. GHYEVAELL 728-736NP_003738.1 SEQ ID NO. 50 TNKS 51. LVVYPWTQRF 33-42 NP_000509.1 SEQ IDNO. 51 HBB 52. MHLRQYELL 386-393 NP_000507.1 SEQ ID NO. 52 GNAS 53.EAIEQILKY 149-157 NP_060600.1 SEQ ID NO. 53 FLJ10539 54. DVAEGDLIEHF108-118 NP_006796.1 SEQ ID NO. 54 HNRPA0 55. DVLQKIKY 191-198NP_060199.2 SEQ ID NO. 55 EPS8L1 56. DSFPMEIRQY 24-33 NP_009330.1 SEQ IDNO. 56 STAT1 57. DVISNIETF 281-289 NP_000337.1 SEQ ID NO. 57 SOX9 58.DVIRLIMQY 9-17 NP_060695.1 SEQ ID NO. 58 SMU-1 59. DVIERVIQY 792-800NP_056199.1 SEQ ID NO. 59 IDN3 60. DVIAQGIGKL 53-62 NP_000995.1 SEQ IDNO. 60 RPLP2 61. DVFNEKGWNY 94-103 NP_005737.1 SEQ ID NO. 61 PBEF1 62.THLDSVTKI 254-262 NP_077308.1 SEQ ID NO. 62 C6.1A 63. DVAGIIADY 294-302XP_048675.4 SEQ ID NO. 63 KIAA1238 64. TAAPFPFHL 536-544 NP_005985.2 SEQID NO. 64 TBX2 65. DTLDKVFTY 86-94 NP_004448.2 SEQ ID NO. 65 ACSL3 66.DTISPTLGF 42-50 NP_001658.1 SEQ ID NO. 66 ARL2 67. DTGILDSIGRF 35-45NP_002376.1 SEQ ID NO. 67 MBP 68. VVYPWTQRF 34-42 NP_000509.1 SEQ ID NO.68 HBB 69. EVVAGIKEYF 128-137 NP_006783.2 SEQ ID NO. 69 MORF4 70.SSVPGVRLL 72-80 NP_003371.1 SEQ ID NO. 70 VIM 71. SVVDAIGISRF 364-374BAC86883.1 SEQ ID NO. 71 FLJ45273 72. EVIPPMKEF 115-123 NP_002484.1 SEQID NO. 72 NDUFB6 73. EVIPPYYSY 152-160 NP_057698.2 SEQ ID NO. 73 TTRAP74. EVNGLISMY 284-292 NP_004238.2 SEQ ID NO. 74 U5-116KD 75. EVIDLMIKEY57-66 NP_060758.1 SEQ ID NO. 75 PHF10 76. EVVAGIKEY 128-136 NP_006783.2SEQ ID NO. 76 MORF4 77. EVFPLAMNY 76-84 NP_444284.1 SEQ ID NO. 77 CCND178. EVVERVLTF 28-36 NP_036302.1 SEQ ID NO. 78 FBXO22 79. SHSPFGLDSF1251-1260 NP_057688.2 SEQ ID NO. 79 JMJD1B 80. FGVDRAILY 457-465NP_002201.1 SEQ ID NO. 80 ITGAV 81. SHSDYLLTI 76-84 NP_003868.1 SEQ IDNO. 81 SOCS2 82. SHLDYDITL 511-519 XP_087353.5 SEQ ID NO. 82 KIAA079483. SHFVSDVVI 63-71 NP_006089.1 SEQ ID NO. 83 GNB2L1 84. EVTELLARY155-163 NP_002686.2 SEQ ID NO. 84 POLR2E 85. ETADTLMGLRY 425-435NP_002047.1 SEQ ID NO. 85 GFPT1 86. EHAHLIVVL 662-670 NP_062570.1 SEQ IDNO. 86 ABCB9 87. EHSLVIDTL 53-61 NP_036526.2 SEQ ID NO. 87 PFDN2 88.EIAEAYLGY 129-137 NP_005336.2 SEQ ID NO. 88 HSPA1A 89. EIYGGSDSRF 42-51NP_036565.1 SEQ ID NO. 89 SF3B1 90. ELIAKIPNF 73-81 NP_003002.1 SEQ IDNO. 90 SET 91. EVIKNFIQY 50-58 NP_057175.1 SEQ ID NO. 91 EIF3S6IP 92.ETADTLLALRY 426-436 NP_005101.1 SEQ ID NO. 92 GFPT2 93. EVVSEPFRSF581-590 NP_002799.3 SEQ ID NO. 93 PSMD2 94. ETFDAGLQAF 2019-2028NP_003118.1 SEQ ID NO. 94 SPTAN1 95. SHSQLMQLI 164-172 NP_008933.2 SEQID NO. 95 ADRM1 96. ETVRELTEF 255-263 NP_006229.1 SEQ ID NO. 96 PPARD97. EVAATEIKM 10-18 NP_005959.2 SEQ ID NO. 97 HNRPM 98. EVAAVLLHF214-222 NP_006535.1 SEQ ID NO. 98 SEC10L1 99. EVFDKTYQF 132-140NP_149103.1 SEQ ID NO. 99 C6orf153 100. ELVKRILNF 174-182 NP_003463.1SEQ ID NO. 100 DEK 101. AHDDGRWSL 95-103 NP_003079.1 SEQ ID NO. 101FSCN1 102. SVVSVISRF 4-12 NP_001335.1 SEQ ID NO. 102 DAD1 103. SVVELINHY132-140 NP_003620.2 SEQ ID NO. 103 PIK3R3 104. SVVDLINHY 397-405NP_005018.1 SEQ ID NO. 104 PIK3R2 105. AHVDLIEKL 51-59 NP_066951.1 SEQID NO. 105 POLR2L 106. FHNELLTQL 97-105 NP_006331.1 SEQ ID NO. 106BAIAP2 107. SVIEAVAHF 812-820 NP_056070.1 SEQ ID NO. 107 C6orf133 108.GHFEKPLFL 149-157 NP_006693.2 SEQ ID NO. 108 NTE 109. GHDASQITL 273-281NP_057481.2 SEQ ID NO. 109 TH1L 110. SAVDFIRTL 293-301 NP_004751.1 SEQID NO. 110 STK17A 111. ISTPVIRTF 989-997 NP_055427.2 SEQ ID NO. 111C9orf10 112. GVIEKLLTSY 28-37 AAH32446 SEQ ID NO. 112 D1S155E 113.SHDLTLVNL 395-403 NP_085139.1 SEQ ID NO. 113 KIAA1706 Sequence of JY114. FPSLREAAL 294-302 NP_004979.2 SEQ ID NO. 114 MAGEA1 Sequences ofRCC075 115. SIFKQPVTK 250-258 NP_003918.1 SEQ ID NO. 115 MBD2 116.KPNANRIAL 139-147 NP_002297.1 SEQ ID NO. 116 LGALS3 117. KLYEMILKR174-182 NP_005728.2 SEQ ID NO. 117 ARL7 118. SLFSRLFGK 7-15 NP_001651.1SEQ ID NO. 118 ARF4 119. KLFDKLLEY 309-317 NP_006586.1 SEQ ID NO. 119API5 120. SLFPNSPKWTSK 96-107 NP_002414.1 SEQ ID NO. 120 MMP7 121.LESLDQLEL 29-37 NP_004273.1 SEQ ID NO. 121 BAG2 122. VVNKVPLTGK 101-110NP_689474.1 SEQ ID NO. 122 MGC17943 123. SVYDSVLQK 4470-4478 NP_149062.1SEQ ID NO. 123 SYNE1 124. SVYVLVRQK 39-47 NP_115604.1 SEQ ID NO. 124MLSTD2 125. ILENIQRNK 557-565 NP_000391.1 SEQ ID NO. 125 ERCC2 126.GSYNKVFLAK 146-155 NP_002803.1 SEQ ID NO. 126 PSMD8 127. TESGLNVTL 6-14NP_006187.1 SEQ ID NO. 127 PCBP1 128. TEHGVEVVL 612-620 NP_005480.1 SEQID NO. 128 SH2D3C 129. TEARFGAQL 327-335 NP_002267.2 SEQ ID NO. 129KRT19 130. TLADILLYY 114-122 NP_004271.1 SEQ ID NO. 130 EEF1E1 131.LVFPSEIVGK 133-142 NP_001002.1 SEQ ID NO. 131 RPS7 132. VLFGKALNPK709-718 NP_003777.2 SEQ ID NO. 132 ABCC3 133. RPELVRPAL 91-99NP_003730.4 SEQ ID NO. 133 AKR1C3 134. VPNQKRLTLL 576-585 NP_004449.1SEQ ID NO. 134 ACSL4 135. QLYWSHPRK 5-13 NP_001023.1 SEQ ID NO. 135RPS29 136. SVYVYKVLK 39-47 NP_059141.1 SEQ ID NO. 136 H2BFS 137.REKLQEEML 186-194 NP_003371.1 SEQ ID NO. 137 VIM 138. RVFSGLVSTGLK415-426 NP_001952.1 SEQ ID NO. 138 EEF2 139. KPRDVSSVEL 1939-1948NP_003119.1 SEQ ID NO. 139 SPTBN1 140. NEFPEPIKL 184-192 NP_004628.4 SEQID NO. 140 RAB7 141. KTYGEIFEK 106-114 NP_004540.1 SEQ ID NO. 141 NDUFC2142. RILFFNTPK 196-204 NP_002803.1 SEQ ID NO. 142 PSMD8 143. RVFPWFSVK1764-1772 NP_005924.1 SEQ ID NO. 143 MLL 144. SEVQDRVML 54-62NP_057145.1 SEQ ID NO. 144 CGI-127 145. SLWDRLIFH 410-418 NP_001986.2SEQ ID NO. 145 ACSL1 146. KVYNIQIRY 468-476 NP_005556.1 SEQ ID NO. 146LCP2 147. RLLEMILNK 171-179 NP_001345.1 SEQ ID NO. 147 AKR1C2 148.SEDKKNIIL 41-49 NP_005498.1 SEQ ID NO. 148 CFL1 149. YEELVRMVL 106-114NP_524147.1 SEQ ID NO. 149 MYL6 150. GEITGEVHM 1758-1766 NP_001448.1 SEQID NO. 150 FLNB 151. IVAGSLITK 183-191 AAH11788 SEQ ID NO. 151 FNBP3152. APRIITGPAPVL 225-236 NP_006766.1 SEQ ID NO. 152 QKI 153. GLASFKSFLK74-83 NP_003608.1 SEQ ID NO.153 RGS5 154. FPNSPKWTSK 98-107 NP_002414.1SEQ ID NO. 154 MMP7 155. FVIETARQL 49-57 NP_078772.1 SEQ ID NO. 155C14orf4 156. IEVDGKQVEL 46-55 NP_001655.1 SEQ ID NO. 156 RHOA 157.GELTGEVRM 1776-1786 NP_001449.1 SEQ ID NO. 157 FLNC 158. GESDDSILRL63-72 NP_001015.1 SEQ ID NO. 158 RPS21 159. GEGDFLAEGGGV 23-34NP_000499.1 SEQ ID NO. 159 FGA 160. DNFPQSL 690-696 NP_000710.3 SEQ IDNO. 160 CACNA1C 161. GLTDVILYH 269-277 NP_006363.3 SEQ ID NO. 161SYNCRIP 162. AALVASGVALY 247-257 NP_002557.2 SEQ ID NO. 162 P2RY11 163.AEIRHVLVTL 107-116 NP_066299.2 SEQ ID NO. 163 MYL6 164. AEPEEVEVL 10-18NP_150638.1 SEQ ID NO. 164 PGR1 165. AIIDHIFASK 256-265 NP_787062 SEQ IDNO. 165 KIS 166. ALLDGSNVVFK 48-58 NP_055075.1 SEQ ID NO. 166 HKE2 167.AMLDTVVFK 302-310 NP_005796.1 SEQ ID NO. 167 PSMD14 168. APARLFALL 2-10NP_002990.2 SEQ ID NO. 168 SDC4 169. AVNAHSNILK 248-257 NP_006830 SEQ IDNO. 169 IMMT 170. APRPGVLLL 8-16 NP_000492 SEQ ID NO. 170 ELN 171.EAFPLRVID 749-757 NP_006113.1 SEQ ID NO. 171 MAN2A2 172. GVADKILKK211-219 NP_004679.1 SEQ ID NO. 172 NMI 173. AVFPKPFVEK 189-198NP_055474.2 SEQ ID NO. 173 KIAA0377 174. VVYVGGILTK 258-267 NP_003351.2SEQ ID NO. 174 UGT8 175. HLEDIVRQK 1751-1759 XP_376178.1 SEQ ID NO. 175TRIP12 176. VTLTLVILSY 207-216 XP_372460.1 SEQ ID NO. 176 LOC390323 177.SLLSLVTGLK reading frame +3 CD105815 SEQ ID NO. 177 Symbol does notexist; Gene type: expressed sequence tag 178. QTYVGITEK 687-695NP_054733.2 SEQ ID NO. 178 U5-200KD 179. HEDKIRVVL 210-218 NP_055416.2SEQ ID NO. 179 EHD2 180. QISIPFLLK 208-216 AAH01979 SEQ ID NO. 180C9orf88 181. GLMGFIVYK 39-37 NP_004885.1 SEQ ID NO. 181 C14orf2 182.FADQEVRSL 950-958 NP_002636.1 SEQ ID NO. 182 PIK3C2A 183. IVALILSTK147-155 NP_001685.1 SEQ ID NO. 183 ATP6V0C 184. GTYAPAEVPK 22-31NP_001344.2 SEQ ID NO. 184 AKR1C1 185. GTMTGMLYK 161-169 NP_006318.1 SEQID NO. 185 TIMM23 186. SLAEILLKK 439-447 NP_006381.1 SEQ ID NO. 186 IPO8187. KLTYIYIQK Reading frame +1 AA295205 SEQ ID NO. 187 Symbol does notexist; Gene type: expressed sequence tag 188. KLLNYAPLEK 58-67 NP_055427SEQ ID NO. 188 POLR2L 189. GTLPHPLQR 182-190 NP_001029.1 SEQ ID NO. 189SCNN1A 190. GLYEFFRAK 680-688 NP_006378.2 SEQ ID NO. 190 CHERP 191.KEPEINTTL 226-234 NP_689939.1 SEQ ID NO. 191 FLJ34588 192. HASDRIIAL330-338 NP_001055.1 SEQ ID NO. 192 TKT Sequences of RCC098 193.RPTLWAAAL 5-13 NP_000589.1 SEQ ID NO. 193 IGFBP3 194. APSPRPLSL 11-19NP_778148.1 SEQ ID NO. 194 C19orf28 195. ASDFITKMDY 362-371 NP_000168.1SEQ ID NO. 195 GSN 196. EERVINEEY 13-21 NP_005601.1 SEQ ID NO. 196 RBBP4197. ATGSWDSFLK 328-337 NP_002065.1 SEQ ID NO. 197 GNB1 198. RMFDMGFEY411-419 NP_031398.2 SEQ ID NO. 198 DDX42 199. APLLRWVL 265-272NP_002124.1 SEQ ID NO. 199 HMOX1 200. ALRPSTSRSLY 43-53 NP_003371.1 SEQID NO. 200 VIM 201. RQIPYTMMK 225-233 NP_002626.1 SEQ ID NO. 201 SLC25A3202. AETHIVLLF 267-275 NP_115497.3 SEQ ID NO. 202 DKFZpS64K142 203.RVHAYIISY 305-313 NP_055416.2 SEQ ID NO. 203 EHD2 204. AVIVLVENFYK 11-21NP_525127.1 SEQ ID NO. 204 S100A16 205. SEELLREHY 61-69 NP_002504.2 SEQID NO. 205 NME3 206. RADGNFLLY 368-376 XP_047214.6 SEQ ID NO. 206KIAA0930 207. SEFTGVWKY 83-91 NP_037364.1 SEQ ID NO. 207 PDCD6 208.SIDRTVMYY 389-397 NP_000332.1 SEQ ID NO. 208 SLC3A1 209. ETDLLDIRSEY463-473 NP_001148.1 SEQ ID NO. 209 ANXA11 210. ESYEALPQH 397-405NP_001370.1 SEQ ID NO. 210 DNMT1 211. SEEEIREAF 82-90 NP_001734.1 SEQ IDNO. 211 CALM2 212. KVMQQNLVY 329-337 NP_006362.1 SEQ ID NO. 212 CRTAP213. DEKSIITY 262-269 NP_003119.1 SEQ ID NO. 213 SPTBN1 214. EEIEGFRY421-428 NP_061955.1 SEQ ID NO. 214 DDX56 215. MENLFINRF 186-194NP_000689.1 SEQ ID NO. 215 ALOX5 216. MEKIWHHTF 82-90 NP_001092.1 SEQ IDNO. 216 ACTB 217. MEHAMETMMF 5-14 NP_002957.1 SEQ ID NO. 217 S100GA10218. EEIFNLKF 353-542 NP_001509.2 SEQ ID NO. 218 GTF2I 219. LVLMVLYLI153-161 NP_660150.1 SEQ ID NO. 219 PIGM 220. EELQQKVSY 285-293NP_003141.2 SEQ ID NO. 220 STAT3 221. LRVAPEEHPVL 94-104 NP_001092.1 SEQID NO. 221 ACTB 222. DGHLFQVEY 13-21 NP_002783.1 SEQ ID NO. 222 PSMA7223. LAELAHREY 14-22 NP_003596.2 SEQ ID NO. 223 OGT 224. NEADVHGIYF651-660 NP_000087.1 SEQ ID NO. 224 CP 225. KVFQEPLFY 114-122 NP_001903.1SEQ ID NO. 225 CTSL 226. GVLAWVKEK 171-179 NP_004212.3 SEQ ID NO. 226NK4 227. HEALLYYVL 738-746 NP_056002.1 SEQ ID NO. 227 KIAA0746 228.HEMIILKL 3489-3496 XP_290768.3 SEQ ID NO. 228 KIAA1554 229. IVPANFPSL443-451 NP_116212.3 SEQ ID NO. 229 C9orf3 230. HLDLGILYY 162-170NP_001373.2 SEQ ID NO. 230 DPAGT1 231. ITDSAGHILY 76-85 NP_006818.2 SEQID NO. 231 TMP21 232. HTDDPLTWDY 267-276 NP_060898.1 SEQ ID NO. 232HCA66 233. IARNLTQQL 313-321 NP_001113.2 SEQ ID NO. 233 ADFP 234.IDQTALAVY 1087-1095 NP_003282.1 SEQ ID NO. 234 TPP2 235. LEDVVIERY 41-49NP_068758.2 SEQ ID NO. 235 FKBP10 236. QIASFILLR 316-324 NP_060796.1 SEQID NO. 236 HIMAP4 237. DEHYILTF 550-557 NP_078862.2 SEQ ID NO. 237OSBPL9 238. DEIGLPKIFY 124-133 NP_003861.1 SEQ ID NO. 238 IQGAP1 239.DEIVRINGY 132-140 NP_005700.1 SEQ ID NO. 239 USH1C 240. DEKLLYDTF112-120 NP_005841.1 SEQ ID NO. 240 SF3B4 241. RIIEETLALK 9-18NP_005722.1 SEQ ID NO. 241 ARPC2 242. GTDELRLLY 107-115 NP_112483.1 SEQID NO. 242 FLJ12525 243. DELEIIEGMKF 209-219 NP_002147.2 SEQ ID NO. 243HSPD1 244. QVDPLSALKY 649-658 NP_037387.2 SEQ ID NO. 244 MKLN1 245.DELHYLEVY 72-80 NP_060676.2 SEQ ID NO. 245 VPS35 246. EEFELLGKAY 81-90NP_003743.1 SEQ ID NO. 246 EIF3S8 247. QLEDGRTLSDY 49-59 NP_061828.1 SEQID NO. 247 UBB 248. DEFLWREQF 42-50 NP_061871.1 SEQ ID NO. 248 FBXW5249. DEMLSRGF 185-192 NP_001407.1 SEQ ID NO. 249 EIF4A1 250. DEPLLKHWEF196-205 NP_061984.1 SEQ ID NO. 250 HLA-DRA 251. PSRDSLPLPV 418-427NP_056412.2 SEQ ID NO. 251 GPSM1 252. NLRETNLDSLP 422-432 NP_003371.1SEQ ID NO. 252 VIM 253. DEVKFLTVL 191-199 NP_001144.1 SEQ ID NO. 253ANXA4 254. NEVEKTMEY 440-448 NP_114130.3 SEQ ID NO. 254 RSHL2 255.DEVQVVRGHY 53-62 NP_000978.1 SEQ ID NO. 255 RPL26 256. DEWLKPELF 296-304NP_057038.1 SEQ ID NO. 256 CGI-26 257. DEYSLVREL 125-133 NP_006280.2 SEQID NO. 257 TLN1 258. NEFEATQKL 343-351 NP_005375.1 SEQ ID NO. 258 NFIL3259. DELQQPLEL 704-712 NP_005410.1 SEQ ID NO. 259 STAT2 260. DVVMTQSPLSL20-30 S40322 SEQ ID NO. 260 IGKV@ 261. SEREAIEVF 358-366 NP_004111 SEQID NO. 261 GBP2 262. RYFYHQEEY 21-29 CAA09468 SEQ ID NO. 262 HLA-DRB1263. TSALPIIQK 63-71 NP_001113.2 SEQ ID NO. 263 ADFP 264. RVQEAVESMVK8-18 AAH14975 SEQ ID NO. 264 FLJ14668 265. TVMELVKIIYK 237-247NP_057111.1 SEQ ID NO. 265 LACTB2 266. RLLQKVLAY 103-111 BAA91493 SEQ IDNO. 266 FLJ10211 267. RIHFPLATY 264-272 NP_006073 SEQ ID NO. 267K-ALPHA-1 268. VGGLKNTLVHRL 279-290 NP_695000.1 SEQ ID NO. 268 FLJ31579269. QAQADSLTVY 679-688 AAP97251.1 SEQ ID NO. 269 PCDHB5 270. VLDPYLLKY34-42 NP_057053.1 SEQ ID NO. 270 MRPS17 271. IFSPPFPLFY 83-92 AAK08108.1SEQ ID NO. 271 FKSG63 272. TELLLKEGF 260-268 NP_055205.1 SEQ ID NO. 272SND1 273. GLFEVGAGWIGK 235-246 NP_000405.1 SEQ ID NO. 273 HSD17B4 274.YEYKFGFEL 97-105 NP_006463.2 SEQ ID NO. 274 TXNIP 275. WPLWRLVSL 2-10NP_001702.1 SEQ ID NO. 275 BGN 276. YIDEQFERY 121-129 NP_004395.1 SEQ IDNO. 276 NEDD5 277. YLDEKLALLNA 897-907 NP_003924.2 SEQ ID NO. 277 BAIAP3278. DEHLITFF 1248-1255 NP_054733.2 SEQ ID NO. 278 US-200KD 279.DDFHIYVY 234-241 NP_006708 SEQ ID NO. 279 SPIN 280. APRTVLLLL 5-13AAL30417.1 SEQ ID NO. 280 HLA-A, -B or -C 281. APRTVALTALL 9-19NP_002112 SEQ ID NO. 281 HLA-DPB1 282. FTDVNSILRY 58-67 AAH58921 SEQ IDNO. 282 EPRS 283. YSEEECRQY 61-69 NP_002061.1 SEQ ID NO. 283 GNAI2 284.YSEKIVDMY 134-142 NP_002465.1 SEQ ID NO. 284 MYH11 285. YTDLLRLFEY 68-77NP_002700.1 SEQ ID NO. 285 PPP1CB 286. YVDPQFLTY 341-349 NP_071763.2 SEQID NO. 286 PJA1 287. HERTFLLEY 96-104 NP_067072.2 SEQ ID NO. 287 SNX6288. SSVPGVRLLQDSVDFS 72-88 NP_003371.1 SEQ ID NO. 288 L VIM 289.SLLTSSKGQLQK 369-380 NP_001113.2 SEQ ID NO. 289 ADFP 290. SPRENILVSL281-290 NP_005054.2 SEQ ID NO. 290 SCD 291. DEVDIKSRAAY 18-28XP_051200.4 SEQ ID NO. 291 FTO 292. TSPSQSLFY 154-162 AAH41787.1 SEQ IDNO. 292 SLC11A1 293. YTETEPYHNY 392-401 NP_653205.2 SEQ ID NO. 293LOC124245 294. SSVPGVRLLQDSVDF 72-86 NP_003371.1 SEQ ID NO. 294 VIM 295.VALISPKDI Reading frame −1 AC079587.4 SEQ ID NO. 295 Symbol does notexist; Gene type: expressed sequence tag 296. STDKAEYTFY 332-341NP_005340.2 SEQ ID NO. 296 RBPSUH 297. VTEIFRQAF 250-258 BAA74907.1 SEQID NO. 297 GARNL1 298. SVLSPLLNK 380-388 NP_004438.2 SEQ ID NO. 298 EPS8Sequences of RCC100 299. RAFSSLGLLK 615-624 NP_003352.1 SEQ ID NO. 299UMOD 300. FSKLRPLISK 243-252 NP_736609.1 SEQ ID NO. 300 PGBD3 301.RTFTWLVGK 353-361 NP_203693.2 SEQ ID NO. 301 MYO1C 302. KVANIILSY1273-1281 NP_079413.2 SEQ ID NO. 302 FLJ21439 303. TMLARLASA 21-29NP_001888.1 SEQ ID NO. 303 CSPG4 304. HELPLPHSV 39-47 NP_001421.2 SEQ IDNO. 304 EPAS1 Sequences of RCC103 305. AVQRTLLEK 177-185 NP_002405.1 SEQID NO. 305 CD99 306. ETRPAGDGTFQKW 256-268 NP_002107 SEQ ID NO. 306HLA-A 307. AVLSILPAIFQK 392-403 XP_084530.5 SEQ ID NO. 307 KIAA0033 308.EIAGHIMEF 848-856 NP_055491.1 SEQ ID NO. 308 PUM1 309. ELIRTIMGW 131-139NP_004315.1 SEQ ID NO. 309 BAX 310. EVFPLKVFGY 45-54 AAH29439 SEQ ID NO.310 ZNF258 311. ATPTSPIRVK 856-865 NP_001447.1 SEQ ID NO. 311 FLNA 312.AVLYQPLFDK 107-116 NP_004528.1 SEQ ID NO. 312 NAP1L1 313. EVVDFIQSKI451-460 NP_817092 SEQ ID NO. 313 PPM1G 314. AVQEFGLARFK 142-152NP_037369.1 SEQ ID NO. 314 PX19 315. EAIQDLWQW 282-290 NP_002511.1 SEQID NO. 315 NPM1 316. GVIRSLMAF 60-68 NP_036558.2 SEQ ID NO. 316 SF3B3317. HIISGTCASW 241-250 NP_006463.2 SEQ ID NO. 317 TXNIP 318. GVIDVITKTW261-270 NP_110407.2 SEQ ID NO. 318 MFTC 319. GVIDLIFEK 600-608NP_004944.2 SEQ ID NO. 319 EIF4G1 320. GVCHIFASF 29-37 NP_005608.1 SEQID NO. 320 RPS14 321. GTYVSSVPR 242-250 NP_002110.1 SEQ ID NO. 321HLA-DOA 322. GTAGLLEQWLK 329-339 NP_064572.1 SEQ ID NO. 322 DC12 323.HVITGLLEHY 133-142 NP_612364.1 SEQ ID NO. 323 SCRN2 324. GTADELVLHSW176-186 NP_620149.1 SEQ ID NO. 324 LYPLAL1 325. EIKEVILEF 873-881NP_060154 SEQ ID NO. 325 VPS13C 326. EEASLLHQF 741-749 NP_003119.1 SEQID NO. 326 SPTBN1 327. KLFIGGLSF 15-23 NP_002127.1 SEQ ID NO. 327 HNRPA1328. DVVPAVRKW 134-142 NP_067027.1 SEQ ID NO. 328 MASA 329. DVTGVVRQW200-208 NP_000651.1 SEQ ID NO. 329 TGFB1 330. DVKDYIQEY 2500-2508XP_290768.3 SEQ ID NO. 330 KIAA1554 331. DVIDNDSWRLW 207-217 NP_006443.1SEQ ID NO. 331 PAICS 332. DVFSSKGMTRW 90-100 NP_803876.1 SEQ ID NO. 332RASSF6 333. DTVKKIESF 3197-3205 NP_006258.2 SEQ ID NO. 333 RANBP2 334.DLPSNHVIDRW 211-221 NP_006100.2 SEQ ID NO. 334 SKB1 335. DLIGHIVEF726-734 NP_056132.1 SEQ ID NO. 335 PUM2 336. DKESQLEAY 106-114NP_872387.1 SEQ ID NO. 336 LOC284680 337. EVIKLKGYTSW 240-250NP_005557.1 SEQ ID NO. 337 LDHA 338. GSSDVIIHR 519-527 XP_290536.2 SEQID NO. 338 KIAA1542 339. GTLDYILQR 158-166 XP_051200.4 SEQ ID NO. 339FTO 340. EVDKRVHMTW 326-335 NP_002808.2 SEQ ID NO. 340 PSMD13 341.SVPYFLFQHW 197-206 NP_003092.3 SEQ ID NO. 341 SOAT1 342. SVEEISTLVQK93-103 NP_115488.2 SEQ ID NO. 342 MRPL43 343. STFQQMWISK 352-361NP_001604.1 SEQ ID NO. 343 ACTA2 344. TTIPHALLTW 1533-1542 NP_006412.1SEQ ID NO. 344 BIG1 345. SAFLLLGLFK 419-428 NP_003181.3 SEQ ID NO. 345TAPBP 346. NIGDEALIGRW 637-647 NP_110428.2 SEQ ID NO. 346 MAGED4 347.TVAFVPISGW 187-196 NP_001393.1 SEQ ID NO. 347 EEF1A1 348. ETVNLRSLGF1930-1939 XP_166300.3 SEQ ID NO. 348 AIM1 349. MPKFSMPGF 72-80BAC87652.1 SEQ ID NO. 349 AHNAK 350. EVMEIMSRF 98-106 NP_006493.1 SEQ IDNO. 350 POLH 351. EVMDVFLRF 695-703 XP_376724.1 SEQ ID NO. 351 CSG1cA-T352. RLQEALNLF 265-273 NP_000507.1 SEQ ID NO. 352 GNAS 353. ETIDWKVFESW174-184 NP_004346.1 SEQ ID NO. 353 CD74 354. ELMEHGVVSW 39-48NP_078988.1 SEQ ID NO. 354 ELMO3 355. ASVAWAVLK 2-10 NP_387504.1 SEQ IDNO. 355 CASPR3 356. SVSPVVHVR 73-81 NP_612403.2 SEQ ID NO. 356 LOC92906357. HVVDRDTEAW 27-36 NP_775898.2 SEQ ID NO. 357 FLJ35220 358. ETITGLRVW6493-6501 NP_004534.1 SEQ ID NO. 358 NEB 359. RQLEDILSTY 77-86NP_787048.1 SEQ ID NO. 359 DKFZp451J0118 360. AIAQAESLRYK 98-108NP_000996.2 SEQ ID NO. 360 RPS3 361. GVLQLGNIVFK 345-355 NP_002464.1 SEQID NO. 361 MYH9 362. EVINALKQTW 489-498 NP_006448.1 SEQ ID NO. 362 LIM363. STAAFFLLR 407-415 NP_001458.1 SEQ ID NO. 363 SLC37A4 364.DIYNFPIHAF 177-186 NP_115898.2 SEQ ID NO. 364 LOC84549 365. TVVERMLSNW1398-1407 BAA21571.1 SEQ ID NO. 365 PLXNB2 366. TKPWFASQIPF 210-220XP_293971.3 SEQ ID NO. 366 LOC345778 Sequences of RCC112 367. GRVDFAYKF111-119 NP_004418.2 SEQ ID NO. 367 PHC2 368. GRDLTDYLM 182-190NP_001605.1 SEQ ID NO. 368 ACTG1 369. GRISITGVGF 101-110 NP_612501.3 SEQID NO. 369 MGC21644 370. GRIVTLISF 262-270 NP_068779.1 SEQ ID NO. 370MCL1 371. GRLDLQYAKL 622-631 NP_000436.1 SEQ ID NO. 371 PLEC1 372.GRTNLIVNY 18-26 NP_001410.2 SEQ ID NO. 372 ELAVL1 373. RYFDTAVSR 5-13AAC17722 SEQ ID NO. 373 HLA-A, -B or -C 374. GRMVQVHEL 170-178NP_006355.2 SEQ ID NO. 374 SEC23A 375. FLDASGAKLDY 53-63 NP_055485.2 SEQID NO. 375 BZW1 376. ATDYHVRVY 348-356 NP_073600.2 SEQ ID NO. 376 FAD104377. ARLPWAGQL 624-632 NP_065385.2 SEQ ID NO. 377 PBXIP1 378. YGMPRQIL192-199 NP_003555.1 SEQ ID NO. 378 TAGLN2 379. GRLLVATTF 385-393NP_002152.1 SEQ ID NO. 379 IARS 380. AGGDWFTSR 136-144 NP_055040.2 SEQID NO. 380 PPP2R1A 381. GRAPISNPGM 179-188 NP_002937 SEQ ID NO. 381 RPA2382. GRMENLASYR 308-317 NP_005389 SEQ ID NO. 382 PPP1R3C 383. VLPKSRVEL89-97 BAA81787 SEQ ID NO. 383 HLA-DOA 384. DAKIRIFDL 28-36 NP_006004.1SEQ ID NO. 384 RPL10 385. GRAMVARLGL 2-11 NP_037362.1 SEQ ID NO. 385CD24 386. FIDASRLVY 612-620 NP_001894.1 SEQ ID NO. 386 CTNNA1 387.DPMKARVVL 21-29 NP_003124.1 SEQ ID NO. 387 SRP9 388. FRFDPQFAL 77-85XP_371812 SEQ ID NO. 388 HLA-DQA1 389. DTDHYFLRY 165-173 NP_057021.2 SEQID NO. 389 PIGT 390. ELLIRKLPF 60-68 NP_003484.1 SEQ ID NO. 390 HIST3H3391. EAFVRHIL 142-149 NP_066299.2 SEQ ID NO. 391 MYL6 392. RYFDTAMSR5-13 AAB48498.1 SEQ ID NO. 392 HLA-A,-B or -C 393. GRVFIISKY 416-424NP_689971 SEQ ID NO. 393 FLJ31657 394. TFRPAAMLVER 154-164 NP_002283.2SEQ ID NO. 394 LAMB2 395. YLLEKSRAI 257-265 NP_002464.1 SEQ ID NO. 395MYH9 396. LSDLGKLSY 353-361 NP_115564.1 SEQ ID NO. 396 MYST1 397.VTDSIRDEY 258-266 NP_005681.1 SEQ ID NO. 397 DNM1L 398. LTDRELEEY567-575 NP_001110.2 SEQ ID NO. 398 ADD1 399. LTDRGVMSY 252-260NP_001562.1 SEQ ID NO. 399 IRF3 400. KGLSVFLNR 527-535 NP_002501.1 SEQID NO. 400 GPNMB 401. VTDNRAFGY 128-136 NP_001334.1 SEQ ID NO. 401 DAB2402. STDVSDLLHQY 257-267 NP_004150.1 SEQ ID NO. 402 PSMB8 403. RSLPFFSAR135-143 NP_067033.1 SEQ ID NO. 403 TRAPPC1 404. YRFMGTEAY 378-386NP_000332.1 SEQ ID NO. 404 SLC3A1 405. MPLLRQEEL 394-402 NP_055416.2 SEQID NO. 405 EHD2 406. VTEIDQDKY 2380-2388 NP_001447.1 SEQ ID NO. 406 FLNA407. MRHLGAFLF 1-9 NP_000346.2 SEQ ID NO. 407 TCN2 408. TTEESLRNYY 20-29NP_002128.1 SEQ ID NO. 408 HNRPA2B1 409. MRTSYLLLF 1-9 NP_005209.1 SEQID NO. 409 DEFB1 410. TVDQVKDLY 882-890 NP_000087.1 SEQ ID NO. 410 CP411. MRYVASYLL 1-9 NP_000995.1 SEQ ID NO. 411 RPLP2 412. VGLIRNLAL511-519 NP_001895.1 SEQ ID NO. 412 CTNNB1 413. GRLDAVLQR 317-325NP_002666.1 SEQ ID NO. 413 PML 414. LLDQGQLNKY 421-430 NP_004850.1 SEQID NO. 414 CLTC 415. NRFAGFGIGL 98-107 NP_620128.1 SEQ ID NO. 415LOC91137 416. KRLGTLVVTY 305-314 NP_443173.2 SEQ ID NO. 416 GBP4 417.KRGDVIYIL 319-327 NP_003921.2 SEQ ID NO. 417 SCAP2 418. SRFDIPLGL1103-1111 NP_056969.2 SEQ ID NO. 418 PCF11 419. STDPSVLGKY 101-110NP_005515.1 SEQ ID NO. 419 HES1 420. SRFLKSDLF 130-138 NP_002916.1 SEQID NO. 420 RGS10 421. VQKPSYYVR 211-219 NP_001113.2 SEQ ID NO. 421 ADFP422. SRISLPLPNF 409-418 NP_003371.1 SEQ ID NO. 422 VIM 423. LRSGLPLLL231-239 NP_004790.1 SEQ ID NO. 423 MADHIP 424. SFKDYIQER 330-338NP_005230.1 SEQ ID NO. 424 ETS2 425. HTQGPVDGSLY 104-114 NP_073585.6 SEQID NO. 425 TENS1 426. STDKFKTDFY 271-280 NP_006824.2 SEQ ID NO. 426COPS6 Sequences of RCC115 427. GSHSMRYFF 25-33 NP_002107 SEQ ID NO. 427HLA-A 428. GSHSMRYFFT 25-34 NP_002107 SEQ ID NO. 428 HLA-A 429.GSHSMRYFH 25-33 I37515 SEQ ID NO. 429 HLA-B 430. AAILGMHNL 135-143NP_055362.1 SEQ ID NO. 430 TMOD3 431. KLDPTKTTL 275-283 NP_006087.2 SEQID NO. 431 NDRG1 432. FVHDLVLYL 783-791 NP_001826.1 SEQ ID NO. 432CLTCL1 433. FVHDLVL 783-789 NP_001826.1 SEQ ID NO. 433 CLTCL1 434.VLIPKLPQL 134-142 NP_644809.1 SEQ ID NO. 434 ORMDL3 435. NEITIPVTF177-185 NP_001531.1 SEQ ID NO. 435 HSPB1 436. YLADFLLTK 255-263NP_006623.1 SEQ ID NO. 436 SLC17A3 437. YLIPLLERL 139-147 NP_004388.1SEQ ID NO. 437 DDX6 438. NEVVTREY 18-25 NP_000984.1 SEQ ID NO. 438 RPL31439. DEFKIGELF 145-153 NP_008835 SEQ ID NO. 439 PRKDC 440. IQRTPKIQVYS21-31 NP_004039.1 SEQ ID NO. 440 B2M 441. LTGPVMPVR 150-158 NP_000968.2SEQ ID NO. 441 RPL13 442. AVAIKAMAK 146-154 NP_001961.1 SEQ ID NO. 442EIF5A 443. FVQMMTAK 142-149 NP_008819.1 SEQ ID NO. 443 CALM1 444.ATDPNILGR 4111-4119 NP_008835.5 SEQ ID NO. 444 PRKDC 445. LLLLSIVIL212-220 NP_001391.2 SEQ ID NO. 445 EDG1 446. KLPNFGFVVF 376-385NP_005745.1 SEQ ID NO. 446 G3BP 447. KLSEIDVAL 174-182 NP_079478.1 SEQID NO. 447 EFHD1 448. LAALPHSCL 5-13 NP_003608.1 SEQ ID NO. 448 RGS5449. YSIITPNILRL 26-36 NP_000055.1 SEQ ID NO. 449 C3 450. ALPSRILLWK2-11 NP_115724.1 SEQ ID NO. 450 MGC3047 451. VKGFYPSDIAVE 247-258AAB59393.1 SEQ ID NO. 451 IGHG2 452. FLLDLSRSV 92-100 NP_005290.1 SEQ IDNO. 452 GPR31 453. IIYKGGTSR 545-553 NP_000168.1 SEQ ID NO. 453 GSN 454.IVADHYASY 3-11 AAC41957 SEQ ID NO. 454 MHC class II 455. EVGGEALGRLL23-33 NP_000509.1 SEQ ID NO. 455 HBB 456. RTGPPMGSRF 175-184 NP_071496.1SEQ ID NO. 456 WBSCR1 457. RQIQESVTF 1305-1313 NP_001139.2 SEQ ID NO.457 ANK2 458. RVAPEEHPV 95-103 NP_001092.1 SEQ ID NO. 458 ACTB 459.TLADLLALR 1433-1441 NP_003768.1 SEQ ID NO. 459 DNAH11 460. RVAPEEHPVLLT95-106 NP_001092.1 SEQ ID NO. 460 ACTB 461. TLADIIARL 1487-1495XP_370756.2 SEQ ID NO. 461 KIAA1305 462. RWEDGSPLNF 142-151 NP_005801.2SEQ ID NO. 462 KLRG1 463. YEVSQLKD 468-475 NP_060705.1 SEQ ID NO. 463CNDP2 464. YRDIPELQGF 663-672 NP_076417 SEQ ID NO. 464 AACS 465.YVDGTQFVRF 51-60 BAA04965 SEQ ID NO. 465 HLA-A, -B or -C 466. SLLDEFYKL184-192 NP_005889.3 SEQ ID NO. 466 M11S1 467. HGIDPTGTY 28-36NP_006078.2 SEQ ID NO. 467 TUBB5 468. SLDKFLASVSTVL 125-137 NP_000549.1SEQ ID NO. 468 HBA1 469. SIGERDLIFH 289-298 NP_003911.1 SEQ ID NO. 469TIMELESS 470. SITSVFITK 1788-1796 NP_003487.1 SEQ ID NO. 470 TRRAP 471.FGEHLLESDLF 28-38 NP_001876.1 SEQ ID NO. 471 CRYAB 472. FLDPIKAYL 76-84NP_056049.3 SEQ ID NO. 472 GPR116 473. FLADPSAFVAA 268-278 NP_000993.1SEQ ID NO. 473 RPLP0 474. ITAPPSRVL 20-28 NP_005054.2 SEQ ID NO. 474 SCD475. VLDELKNMKC 170-179 NP_055191.1 SEQ ID NO. 475 CYFIP2 476. LLGPRLVLA23-31 NP_006818.2 SEQ ID NO. 476 TMP21 477. IIMPHNIYL 251-259NP_000569.2 SEQ ID NO. 477 SLC11A1 478. LVRMVLNG 144-151 NP_034990 SEQID NO. 478 MYL6 479. RLYGPSSVSF 133-142 NP_001226.2 SEQ ID NO. 479SERPINH1 480. FEAPIKLVF 236-244 NP_110416.1 SEQ ID NO. 480 HM13 481.IQPGAVKVY 1472-1480 NP_000055.1 SEQ ID NO. 481 C3 482. VLAEVPTQL 501-509NP_003906.1 SEQ ID NO. 482 CPNE1 483. IMRAGMSSL 521-529 NP_001753.1 SEQID NO. 483 CCT6A 484. VEFSSGLKGMSL 96-107 NP_004037.1 SEQ ID NO. 484ATP5A1 485. ILNPDNSFEIL 241-251 NP_001737.1 SEQ ID NO. 485 CANX 486.VALEFALHL 344-352 NP_612384.1 SEQ ID NO. 486 CABLES1 487. TVAVPLVGK22-30 NP_077271.1 SEQ ID NO. 487 MGC3067 488. TLSDLRVYL 121-129NP_542763.1 SEQ ID NO. 488 C20Orf139 489. TLIDIMTRF 35-43 NP_000179.1SEQ ID NO. 489 HK1 Sequences of RCC116 490. HDFPRALIF 64-72 AAH22188 SEQID NO. 490 CG018 491. GSHSMRYF 25-32 BAA04965 SEQ ID NO. 491 HLA-A, -Bor -C 492. SLMDHTIPEV 289-298 NP_005616.1 SEQ ID NO. 492 SDCBP 493.SGVHTFPAVLQ 155-165 AA022172 SEQ ID NO. 493 Ig heavy chain 494.FLVTVIHTL 1065-1073 NP_005752.1 SEQ ID NO. 494 PLXNC1 495. TDGKVFQF24-31 NP_000977.1 SEQ ID NO. 495 RPL24 496. YDLLRNTNF 246-254NP_001387.2 SEQ ID NO. 496 DYRK1A 497. ILYPKTLFL 138-146 NP_000935.1 SEQID NO. 497 PPP3CA 498. MRYVASYL 1-8 NP_000995.1 SEQ ID NO. 498 RPLP2499. FIWENIHTL 3725-3733 NP_056363.2 SEQ ID NO. 499 BPAG1 500. RELPAWVSF125-133 NP_056107.1 SEQ ID NO. 500 MBC2 501. QDLNRIFPL 81-89 NP_002718.2SEQ ID NO. 501 PRG1 502. RDSIVAEL 97-104 NP_009194.2 SEQ ID NO. 502 COPE503. ADVLKVEVF 130-138 NP_002203.1 SEQ ID NO. 503 ITGB4BP 504. YDSIIYRM335-342 NP_005756.2 SEQ ID NO. 504 ATP6AP2 505. AMNPVEHPF 203-211NP_000964.1 SEQ ID NO. 505 RPL8 506. SELIRNVTL 126-134 NP_004238.2 SEQID NO. 506 U5-116KD 507. QDVARVLGF 117-125 NP_006020.3 SEQ ID NO. 507PNMA1 508. SDHIHIIAL 215-223 NP_060140.1 SEQ ID NO. 508 OTUB1 509.ADSLRLQQL 781-789 NP_003118.1 SEQ ID NO. 509 SPTAN1 510. LLDIRSEY466-473 NP_001148.1 SEQ ID NO. 510 ANXA11 511. VLFGLLREV 663-671NP_054722.2 SEQ ID NO. 511 DHX38 512. VAVGRALYY 510-518 NP_001914.2 SEQID NO. 512 DDB1 513. MRFLAATFL 1-9 NP_006423.1 SEQ ID NO. 513 NPC2 514.YTDPEVFKY 398-406 NP_000952.1 SEQ ID NO. 514 PTGIS 515. HDFLKYDFF232-240 NP_149351.1 SEQ ID NO. 515 SURF4 516. AIDQLHLEY 525-533NP_004915.2 SEQ ID NO. 516 ACTN4 517. SDLERVTSL 316-324 NP_078843.2 SEQID NO. 517 FLJ21616 518. TLLPLRVFL 128-136 NP_699196.1 SEQ ID NO. 518FLJ90013 519. YSIITPNILR 26-35 NP_000055.1 SEQ ID NO. 519 C3 520.FELQRNFQL 19-27 NP_057246.2 SEQ ID NO. 520 ING4 521. LDLQRNYIF 186-194NP_940967.1 SEQ ID NO. 521 UNQ3030 522. RRLDPIPQL 56-64 NP_057211.4 SEQID NO. 522 MGC8721 523. SLPIKESEIIDF 85-96 NP_002943.2 SEQ ID NO. 523RPS2 524. TELLRYYML 292-300 NP_055241.1 SEQ ID NO. 524 SNX5 525.FIYHGEVPQA 254-263 NP_000237.1 SEQ ID NO. 525 MHC2TA 526. AEMLRSISF217-225 NP_001315.1 SEQ ID NO. 526 CSTF1 527. RLQEDPPVGV 15-24NP_003328.1 SEQ ID NO. 527 UBE2B 528. AELERAAAL 465-473 NP_689813.1 SEQID NO. 528 FLJ35453 529. YTDKIDRY 107-114 NP_003262.1 SEQ ID NO. 529TM4SF7 530. FLLPDVIRI 329-337 NP_060671.2 SEQ ID NO. 530 TBC1D13 531.VELPHINLL 169-177 NP_060536.2 SEQ ID NO. 531 FLJ10349 532. VMLDVPIRL725-733 NP_004832.1 SEQ ID NO. 532 RASAL2 533. SLLENLEKI 209-216NP_112604.1 SEQ ID NO. 533 HNRPC 534. YADPVNAHY 226-234 NP_005147.3 SEQID NO. 534 ROD1 535. AELLRGLSL 165-173 NP_036293.1 SEQ ID NO. 535 FBXL5536. TTEVHPELY 51-59 NP_057050.1 SEQ ID NO. 536 SDBCAG84 537. RETNLDSLP424-432 NP_003371.1 SEQ ID NO. 537 VIM 538. ELEDSTLRY 543-551NP_000436.1 SEQ ID NO. 538 PLEC1 Sequences of RCC130 539. FLDIYIFL 84-91XP_372703.1 SEQ ID NO. 539 LOC390875 540. TYTDRVFFL 1282-1290 BAA21S71.1SEQ ID NO. 540 PLXNB2 541. SPHLANYFYF 147-156 BAC87422 SEQ ID NO. 541Symbol does not exist; Gene type: unnamed protein product 542. SPRLPVGGF1921-1929 XP_376178.1 SEQ ID NO. 542 TRIP12 543. KLLDKVQAYS 9-18NP_000156.1 SEQ ID NO. 543 GJA1 544. AYQHLFYLL 955-963 NP_839943.2 SEQID NO. 544 IQGAP3 545. KYILLMDIIA 148-157 NP_005987.2 SEQ ID NO. 545TBX3 546. RYSSMAASF 82-90 NP_005755.1 SEQ ID NO. 546 MAP17 547.SPRAAEPVQL 397-406 NP_001207.1 SEQ ID NO. 547 CA9 548. IYTSSVNRL 535-543NP_004757.1 SEQ ID NO. 548 COPB2 549. LYPQFMFHL 576-584 NP_006355.2 SEQID NO. 549 SEC23A 550. RYIPTAAAF 415-423 NP_037468.1 SEQ ID NO. 550SEC61A1 551. EYIVKKIPV 237-245 NP_001406.1 SEQ ID NO. 551 EIF2S3 552.SRVEAVYVL 13-21 NP_031391.1 SEQ ID NO. 552 PADI2 553. MPRGVVVTL 851-859NP_056197.1 SEQ ID NO. 553 HECTD1 554. LPKPPGRGV 341-349 NP_036294.1 SEQID NO. 554 FBXL6 555. RLWGEPVNL 1665-1673 NP_004643.2 SEQ ID NO. 555USP9X 556. RLLDVLAPL 14-22 NP_569712.1 SEQ ID NO. 556 COL18A1 557.LYILSSHDI 474-482 NP_277041.1 SEQ ID NO. 557 FBXO24 558. TPMGPGRTV235-243 NP_006490.3 SEQ ID NO. 558 LGALS8 559. GPPGTGKTDVAVQI 823-836NP_055506.1 SEQ ID NO. 559 AQR 560. NEIEDTFRQF 46-55 NP_004222.2 SEQ IDNO. 560 ATP6V1F 561. EEIDLRSVGW 315-324 NP_112192.2 SEQ ID NO. 561UNC93B1 562. KYQKGFSLW 245-253 NP_055109.1 SEQ ID NO. 562 TRAM1 563.VYPDGIRHI 519-527 NP_036558.2 SEQ ID NO. 563 SF3B3 564. KFIDTTSKF366-374 NP_005052.1 SEQ ID NO. 564 RPL3L 565. FLDILNTLI 1729-1737NP_001362.1 SEQ ID NO. 565 DNAH8 566. KYITQGQLLQF 200-210 NP_068586.1SEQ ID NO. 566 ELOVL5 567. KYLSVQGQLF 344-353 NP_055156.1 SEQ ID NO. 567MTCH1 568. RYFDEPVEL 355-363 NP_055385.2 SEQ ID NO. 568 ARFGAP3 569.KYDEIFYNL 452-460 NP_055416.2 SEQ ID NO. 569 EHD2 570. SYIEHIFEI 61-69NP_003759.1 SEQ ID NO. 570 PEA15 571. KFIDPIYQVW 572-581 NP_060897.2 SEQID NO. 571 RRN3 572. LGYTEGALLAL 1370-1380 NP_149045.2 SEQ ID NO. 572PCDH15 573. KYPSPFFVF 2-10 NP_085077.1 SEQ ID NO. 573 DHX9 574.EYPDRIMNTF 158-167 NP_006077.1 SEQ ID NO. 574 TUBB4 575. VYISEHEHF107-115 NP_001285.1 SEQ ID NO. 575 CLPTM1 576. KYFLKPEVL 167-175NP_065843.2 SEQ ID NO. 576 KIAA1363 Sequence of JY 577. GPALGRSFL 78-86NP_001243.1 SEQ ID NO. 577 TNFSF7 Sequences of the control peptides 578.ELAGIGILTV 26-35 NP_005502.1 SEQ ID NO. 578 MLANA(modified A27- >L) 579.ILKEPVHGV 896-904 NP_057849.4 SEQ ID NO. 579 pol 580. GILGFVFTL 58-66S14616 SEQ ID NO. 580 Symbol does not exist; Gene type: matrix proteinM1 581. NLVPMVATV 495-503 P06725 SEQ ID NO. 581 Symbol does not exist;Gene type: pp65 582. LLDFVRFMGV 284-293 P03204 SEQ ID NO. 582 Symboldoes not exist; Gene type: EBNA-6 nuclear protein 583. GLCTLVAML 259-267NP_039857.1 SEQ ID NO. 583 Symbol does not exist; Gene type:Immediate-early transactivator 584. CLGGLLTMV 294-302 AAB59844.1 SEQ IDNO. 584 Symbol does not exist; Gene type: latent membrane protein 2 585.APRTVALTA 9-17 NP_002112 SEQ ID NO. 585 HLA-DPB1

1. A tumor-associated peptide with an amino acid sequence selected fromthe group consisting of SEQ ID NO. 1 to SEQ ID NO. 577 from the attachedsequence protocol, the peptide being capable of binding to a molecule ofthe human major histocompatibility complex (MHC) class I.
 2. The peptideaccording to claim 1, characterized by at least one amino acid beingreplaced by another amino acid with similar chemical properties.
 3. Thepeptide according to claim 1, characterized by at least one additionalamino acid being present at the N- or/and C-terminus.
 4. The peptideaccording to claim 1, characterized by at least one amino acid beingdeleted.
 5. The peptide according to claim 1, characterized by at leastone amino acid being chemically modified.
 6. A method for preparing adrug for the treatment of a tumor disease and/or an adenomatous diseasewherein said method comprises administering, to a patient in need ofsuch treatment, a tumor-associated peptide with an amino acid sequenceselected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 577from the attached sequence protocol, the peptide being capable ofbinding to a molecule of the human major histocompatibility complex(MHC) class I.
 7. A method for treating a tumor disease and/or anadenomatous disease wherein said method comprises administering, to apatient in need of such treatment, a tumor-associated peptide with anamino acid sequence selected from the group consisting of SEQ ID NO. 1to SEQ ID NO. 577 from the attached sequence protocol, the peptide beingcapable of binding to a molecule of the human major histocompatibilitycomplex (MHC) class I.
 8. The method according to claim 7, characterizedby the disease being kidney, mammary, pancreas, gastric, brain, bladder,testicular cancer and/or a tumor disease of the nerve system.
 9. Themethod according to claim 7, characterized by the peptide being usedtogether with an adjuvant.
 10. The method according to claim 7,characterized by the peptide being used bound to an antigen presentingcell.
 11. A method for labeling leucocytes wherein said method comprisesthe use of a tumor-associated peptide with an amino acid sequenceselected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 577from the attached sequence protocol, the peptide being capable ofbinding to a molecule of the human major histocompatibility complex(MHC) class I.
 12. The method according to claim 11 for evaluation ofthe course of a therapy for a tumor disease.
 13. A method for productionof an antibody wherein said method comprises the use of atumor-associated peptide with an amino acid sequence selected from thegroup consisting of SEQ ID NO. 1 to SEQ ID NO. 577 from the attachedsequence protocol, the peptide being capable of binding to a molecule ofthe human major histocompatibility complex (MHC) class I.
 14. Apharmaceutical composition comprising a tumor-associated peptide with anamino acid sequence selected from the group consisting of SEQ ID NO. 1to SEQ ID NO. 577 from the attached sequence protocol, the peptide beingcapable of binding to a molecule of the human major histocompatibilitycomplex (MHC) class I.
 15. An entity selected from the group consistingof: A) a nucleic acid molecule encoding a tumor-associated peptide withan amino acid sequence selected from the group consisting of SEQ ID NO.1 to SEQ ID NO. 577 from the attached sequence protocol, the peptidebeing capable of binding to a molecule of the human majorhistocompatibility complex (MHC) class I; B) a vector comprising anucleic acid molecule encoding a tumor-associated peptide with an aminoacid sequence selected from the group consisting of SEQ ID NO. 1 to SEQID NO. 577 from the attached sequence protocol, the peptide beingcapable of binding to a molecule of the human major histocompatibilitycomplex (MHC) class I; and C) a cell that has been genetically alteredusing the nucleic acid molecule of part A, or using the vector of Part Bto produce a tumor-associated peptide with an amino acid sequenceselected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 577from the attached sequence protocol, the peptide being capable ofbinding to a molecule of the human major histocompatibility complex(MHC) class I. 16-17. (canceled)